The aim of the research is to increase the applicability of lipopeptides as drugs.To this end,non-ionic triblock copolymers,namely poloxamers,were applied.The physico-chemical properties of poloxamers vary depending o...The aim of the research is to increase the applicability of lipopeptides as drugs.To this end,non-ionic triblock copolymers,namely poloxamers,were applied.The physico-chemical properties of poloxamers vary depending on the length of the blocks.In our study,we experimented with different types and systematically investigated the variation of the critical micelle concentration(CMC)of poloxamers at 25 and 37°C in different media.In addition,the cytotoxicity of the different poloxamer micelles on three different cell lines was evaluated,and based on the results,Plur104,Plur123,and Plur127 were selected.Fatty acid elongated derivatives of a short antibacterial peptide(pL1),a medium-sized anticancer peptide(pCM15),and a branched-chain vaccine antigen(pATIPC)were used as lipopeptide models,and their formulations with the selected poloxamers were investigated.The solubility and homogeneity of the lipopeptides were significantly increased,and dynamic light scattering(DLS)measurements showed the formation of small particles of around 20 nm,which were well reproducible and storable.Similar homogenous micelle formation was observed after freeze-drying and reconstitution with water.The pL1 lipopeptide,formulated with the selected poloxamers,exhibited enhanced antibacterial activity with significantly reduced haemolytic side effects.The pCM15 peptide,when incorporated into poloxamer micelles,showed significantly enhanced cytotoxicity against tumor cells.Additionally,the internalization rate of poloxamer-formulated pATIPC peptide by antigen-presenting model cells exceeded that of the unformulated peptide.Our results demonstrate the potential of poloxamers as promising tools for the formulation of lipopeptides and for the optimization of their selectivity.展开更多
Chromatographic separation of the marine-derived bacterium Bacillus licheniformis resulted in the isolation of two new cyclic lipopeptides named ai-Cl6 surfactin （1） and ai-Cl4 surfactin （2）, together with iso-Cm5...Chromatographic separation of the marine-derived bacterium Bacillus licheniformis resulted in the isolation of two new cyclic lipopeptides named ai-Cl6 surfactin （1） and ai-Cl4 surfactin （2）, together with iso-Cm5 surfactin and iso-Cl6 surfactin. The structures of the new cyclic lipopeptides were determined through extensive spectroscopic analysis. The sequences of the amino acids in cyclic nucleus were established by the ESI-MS/MS fragmentation, which provided an efficient method to detect lipopeptides from bacterium extracts without senaration展开更多
The integrated lipopeptide(RVA)/gene complexes are fabricated with bi-directional regulation on tumor cells and micro-environment.After self-assembling and target coating modification,the poly(γ-glutamic acid)(γ-PGA...The integrated lipopeptide(RVA)/gene complexes are fabricated with bi-directional regulation on tumor cells and micro-environment.After self-assembling and target coating modification,the poly(γ-glutamic acid)(γ-PGA)/RVA nano-vectors can sequentially respond to pH&redox stimuli,and guarantee efficient therapeutic gene delivery and control release of all-trans retinoic acid.The design provides a facile but promising strategy to treat refractory cancers.展开更多
The multifunctional secondary metabolites known as cyclic lipopeptides(CLPs),which are produced by a large variety of bacteria,have become a key category of plant immunity elicitors.Pseudomonas-CLPs(PsCLPs)are extreme...The multifunctional secondary metabolites known as cyclic lipopeptides(CLPs),which are produced by a large variety of bacteria,have become a key category of plant immunity elicitors.Pseudomonas-CLPs(PsCLPs)are extremely diverse in structure and biological activity.However,an understanding of CLP-plant structure–function interactions currently remains elusive.Here,we identify medpeptin,a novel CLP from Pseudomonas mediterranea that consists of 22 amino acids.Medpeptin is synthesized by a non-ribosomal peptide synthase(NRPS)gene cluster and regulated by a quorum-sensing system.Further research indicates that medpeptin does not exhibit antimicrobial activity;instead,it induces plant cell death immunity and confers resistance to bacterial infection.Comparative transcriptome analysis and virus-induced gene silencing(VIGS)reveal a set of immune signaling candidates involved in medpeptin perception.Silencing of a cell-wall leucine-rich repeat extensin protein(NbLRX3)or a receptor-like protein kinase(NbRLK25)—but not BAK1 or SGT1—compromises medpeptin-triggered cell death and resistance to pathogen infection in Nicotiana benthamiana.Our findings point to a noncanonical mechanism of CLP sensing and suggest perspectives for the development of plant disease resistance.展开更多
Lysobacter harbors a plethora of cryptic biosynthetic gene clusters(BGCs),albeit only a limited number have been analyzed to date.In this study,we described the activation of a cryptic polyketide synthase(PKS)/nonribo...Lysobacter harbors a plethora of cryptic biosynthetic gene clusters(BGCs),albeit only a limited number have been analyzed to date.In this study,we described the activation of a cryptic polyketide synthase(PKS)/nonribosomal peptide synthetase(NRPS)gene cluster(lsh)in Lysobacter sp.DSM 3655 through promoter engineering and heterologous expression in Streptomyces sp.S001.As a result of this methodology,we were able to isolate two novel linear lipopeptides,lysohexaenetides A(1)and B(2),from the recombinant strain S001-lsh.Furthermore,we proposed the biosynthetic pathway for lysohexaenetides and identified LshA as another example of entirely iterative bacterial PKSs.This study highlights the potential of heterologous expression systems in uncovering cryptic biosynthetic pathways in Lysobacter genomes,particularly in the absence of genetic manipulation tools.展开更多
We describe an application of carrier protein-free strategy in constructing a fully synthetic methamphetamine(METH)vaccine that contains three components:Toll-like receptor 2 ligand,Th2 epitope,and METH hapten.The imm...We describe an application of carrier protein-free strategy in constructing a fully synthetic methamphetamine(METH)vaccine that contains three components:Toll-like receptor 2 ligand,Th2 epitope,and METH hapten.The immunological evaluation in mice revealed high titers of METH-specific antibodies induced by the construct and the activation of humoral immunity that would be beneficial for neutralization and clearance of the METH molecule.Behavio ral experiments indicated that the synthetic vaccine attenuated the acquisition of METH-induced conditioned place preference and inhibited the initiation and expression of METH-induced locomotor sensitization.These results demonstrate that the lipopeptide-based vaccine has invo ked an immune response and showed the potential of preventing the rewarding and psychoactive effects of METH.展开更多
Lipopeptides are currently re-emerging as an interesting subgroup in the peptide research field, having historical applications as antibacterial and antifungal agents and new potential applications as antiviral, antit...Lipopeptides are currently re-emerging as an interesting subgroup in the peptide research field, having historical applications as antibacterial and antifungal agents and new potential applications as antiviral, antitumor, immune-modulating and cell-penetrating compounds. However, due to their specific structure, chromatographic analysis often requires special buffer systems or the use of trifluoroacetic acid, limiting mass spectrometry detection. Therefore, we used a traditional aqueous/acetonitrile based gradient system, containing 0.1% （m/v） formic acid, to separate four pharmaceutically relevant lipopeptides （polymyxin B1, caspofungin, daptomycin and gramicidin A1）, which were selected based upon hierarchical cluster analysis （HCA） and principal component analysis （PCA）.In total, the performance of four different C18 columns, including one UPLC column, were evaluated using two parallel approaches. First, a Derringer desirability function was used, whereby six single and multiple chromatographic response values were rescaled into one overall D-value per column. Using this approach, the YMC Pack Pro C18 column was ranked as the best column for general MS-compatible lipopeptide separation. Secondly, the kinetic plot approach was used to compare the different columns at different flow rate ranges. As the optimal kinetic column performance is obtained at its maximal pressure, the length elongation factor λ（Pmax/Pexp） was used to transform the obtained experimental data （retention times and peak capacities） and construct kinetic performance limit （KPL） curves, allowing a direct visual and unbiased comparison of the selected columns, whereby the YMC Triart C18 UPLC and ACE C18 columns performed as best. Finally, differences in column performance and the （dis）advantages of both approaches are discussed.展开更多
Listeria monocytogenes is a worrisome food-borne pathogen threatening global food safety.Our previous study proved that lipopeptide brevilaterin B showed efficient antibacterial activity against L.monocytogenes by int...Listeria monocytogenes is a worrisome food-borne pathogen threatening global food safety.Our previous study proved that lipopeptide brevilaterin B showed efficient antibacterial activity against L.monocytogenes by interacting with the cell membrane.This research further explored the antibacterial mechanism of brevilaterin B against L.monocytogenes at the sub-minimum inhibition concentration via transcriptomic analysis.Brevilaterin B induced growth inhibition rather than direct membrane lysis in L.monocytogenes at the minimum inhibitory concentration.Transcriptomic analysis showed 1779 difference expressed genes,including 895 up-regulated and 884 down-regulated genes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis indicated that brevilaterin B influenced multiple pathways of L.monocytogenes,including peptidoglycan biosynthesis,membrane transport(ATP-binding cassette transports,ion transport),cellular metabolism(amino acid and lipid metabolism),ATP synthesis,and activation of the stress response(quorum sensing and bacterial chemotaxis).In conclusion,brevilaterin B affects gene expression related to biosynthesis,transport and stress response pathways on the membrane of L.monocytogenes.The present work provides the first transcriptomic assessment of the antibacterial mechanism of lipopeptide brevilaterin B at the gene level.展开更多
MALDI-TOF-MS technology was used for identification of lipopeptide antibiotics producedby GEB3 strain, a derivative of Bacillus subtilis 168 which was transformed by lpaB3gene. The result showed GEB3 only produced lip...MALDI-TOF-MS technology was used for identification of lipopeptide antibiotics producedby GEB3 strain, a derivative of Bacillus subtilis 168 which was transformed by lpaB3gene. The result showed GEB3 only produced lipopeptide antibiotic surfactin. The analysisby LC-MS demonstrated that GEB3 produced standard surfactin isoforms with side chainlengths of 13,14 and 15 carbon atoms. The bioactivity detection of surfactin indicatedthat the surfactin produced by GEB3 had inhibition effect on plant pathogens Rhizoctoniasolani and Pyricularia oryzae.展开更多
Agricultural application studies, including field experiments and acute toxicity tests, were conducted for lipopeptides secreted by marine-derived Bacillus marinus B-9987. Benefiting from commercially available scaled...Agricultural application studies, including field experiments and acute toxicity tests, were conducted for lipopeptides secreted by marine-derived Bacillus marinus B-9987. Benefiting from commercially available scaled-up lipopeptide purification, the sample of impurities（isolated from target lipopeptides）, raw extracted sample（purity： 9.08%）, partially purified sample（purity： 20.86%）, and highly purified sample（purity： 87.51%） were prepared from B. marinus B-9987 fermentation broth, and used in lab-scale antagonism tests, field experiments, swarming motility tests, and acute toxicity tests. Operations and conditions in field experiments were consistent with the Pesticide-Guidelines for the Field Efficacy Trials（GB/T 17980.28-2000）, and acute toxicity tests were executed according to Toxicological Test Methods of Pesticides for Registration（GB 15670-1995）. In agar diffusion tests in vitro and pot tests in vivo, all lipopeptide samples with different purities significantly inhibited Botrytis cinerea; meanwhile the sample of impurities isolated from target lipopeptides were not effective against B. cinerea. Results of lab-scale tests showed that the target lipopeptides were effective substances against B. cinerea. Thus, partially purified and raw extracted samples were used in field experiments instead of the highly purified sample for cost saving. In the field experiments against rose grey mold, biological control efficacy of 500 mg L–1 lipopeptides reached 67.53%, slightly lower than 74.05% reached by the agrochemical pyrimethanil. However, pyrimethanil severely suppressed B. marinus B-9987, whereas the lipopeptides promoted swarming motility and biocontrol efficacy of Bacillus biomass. Lipopeptides at 87.51% purity were tested for systemic acute toxicity and confirmed as low-toxicity substances. In conclusion, low-toxicity lipopeptides were potential alternatives to agrochemicals, and they also performed good promotion when combined with homologous biological control microorganism. There were 2 breakthroughs in this research：（1） marine-derived bacterial lipopeptides inhibited grey mold caused by B. cinerea in field experiments; and（2） purified bacterial lipopeptides（sample purity： 〉87.51%） were determined to be low-toxicity substances by systemic acute toxicity tests, satisfying the strict requirement of pesticide registration in China（required purity： 〉85%）. This study provides support for using extracellularBacillus-derived lipopeptides commercially similar to Bacillus-based biological control agents.展开更多
The science and technology interact with the art in several ways. Biotechnological coupled with analytical approaches can play an important role in protecting and preserving cultural heritage for future generations. M...The science and technology interact with the art in several ways. Biotechnological coupled with analytical approaches can play an important role in protecting and preserving cultural heritage for future generations. Many microorganisms influenced by environmental conditions are the main responsible for biological contamination in built heritage. Biocides based on chemical compounds have been used to mitigate this problem. Thus, it is vitally important to develop proper remediation actions based on environmentally innocuous alternative. Bacillus specie is emerging as an optimistic alternative for built heritage treatment due to their capacity to produce secondary metabolites with antagonistic activities against many fungal pathogens. Therefore, the intent of this work was to access a rapid evaluation of antifungal potential of bioactive metabolites produced by Bacillus strains and simultaneously their characterization using spectroscopic (NMR) and chromatographic techniques (LC-ESI-MS). The high antifungal activity obtained for Bacillus sp. active compounds produced in this study confirms the great potential to suppress biodeteriogenic fungi growth on historical artworks. Additionally, the proposed methodology allowed to access bioactive metabolites produced without need of the laborious total previous isolation and could be used as a viable alternative to be employed for screening and production of new green biocides.展开更多
The molar absorption coefficients of each of 14 kinds of amino acids were determined by the spectrophotometric method, and the mean molar absorption coefficients of 37 different mixtures of each with amino acid compos...The molar absorption coefficients of each of 14 kinds of amino acids were determined by the spectrophotometric method, and the mean molar absorption coefficients of 37 different mixtures of each with amino acid composition exactly equivalent to that of the peptide chain of the corresponding lipopeptide were determined based on calculation or experimental. The significance of the results is that the mean molar absorption coefficients strongly demonstrate the regular patterns, though different amino acids bear quite different molar absorption coefficients.展开更多
This paper describes the synthesis of peptide fragments for use in a new type of combinatorial discovery technology, in which the building blocks are brought together by non-covalent interactions, rather than direct c...This paper describes the synthesis of peptide fragments for use in a new type of combinatorial discovery technology, in which the building blocks are brought together by non-covalent interactions, rather than direct chemical bonding. The building blocks of interest—in this case different amino acids—are converted to amphiphiles by attachment to lipid tails. The amphiphiles, when mixed together in aqueous phase, are designed so that they aggregate spontaneously to form micelles. The building blocks form the headgroups of each of the amphiphiles, and these headgroups cover the surface of the micelle in a dynamic close-packed fluid mosaic array. These building blocks come together so closely that two- or three-dimensional structures are created on the surface of the micelles, and these can be screened in biological assays to find out which combination of building blocks is able to elicit a biological response. Lipopeptides consisting of two residues of lipoamino acid and other amino acids moieties have been designed, synthesized, characterized and the ability of these constructs to form supra-molecular assemblies is demonstrated.展开更多
In biological controls using <em>Bacillus</em> spp., cyclic lipopeptides play a role as elicitors to induce disease resistance on various host plants. However, it is still unclear the specificity between c...In biological controls using <em>Bacillus</em> spp., cyclic lipopeptides play a role as elicitors to induce disease resistance on various host plants. However, it is still unclear the specificity between cyclic lipopeptides and host plants to induce disease resistance. In this study, we aimed to clarify the specificity to induce disease resistance among cyclic lipopeptides on various host plants. Our data clearly showed both cyclic lipopeptides conferred disease suppression on most of host plants, but at different range of cyclic lipopeptide concentration. Our findings contribute to understanding the complex on the specificity of cyclic lipopeptide derived induced disease resistance.展开更多
In the last decade,the rise of antibiotic resistance has heightened interest in antimicrobial peptides and lipopeptides as promising alternatives to conventional antibiotics because of their lower propensity to develo...In the last decade,the rise of antibiotic resistance has heightened interest in antimicrobial peptides and lipopeptides as promising alternatives to conventional antibiotics because of their lower propensity to develop resistance.However,lipopeptides often show undesired cytotoxicity due to their non-selective membrane disruptive effect,and their limited aqueous solubility represents a matter of concern from a pharmaceutical point of view.This study demonstrates a panel of ultrashort cationic lipopeptides(USCLs)consisting of a tetrapeptide(L1),originated from buforin II,coupled with saturated fatty acids of different lengths.Our results highlight that the 16-carbon fatty acid lipopeptide(Pal-L1)exhibits relevant antibacterial activity against multiresistant Staphylococcus aureus strain.However,the formation of heterogenic aggregates in cell culturemedium and toxic effects on human cells were also observed.Pal-L1 formulation with the randomly methylatedα-cyclodextrin(RAMEA)and the sulfobutylether-β-cyclodextrin(SBECD)has resulted in a production of ultralow-sized molecular dispersion systems and reduced lipopeptide toxicity without compromising its antimicrobial activity.With titration 1H-NMR,2D NMR experiments,together with molecular dynamics simulations,we described the size,structure,stoichiometry,and dissociation constant of the supramolecular complexes.Interactions of neutral and negatively chargedmodel liposomes with Pal-L1 lipopeptide in the presence or absence of cyclodextrins serve an explanation for the membrane selectivity,and based on the results,we proposed a potential mechanism of action for the Pal-L1+cyclodextrin complexes on different biological membranes.Overall,our model characterization points out that cyclodextrin formulation improves the therapeutical applicability of lipopeptides.展开更多
Biocontrol microorganisms and their derived metabolites with antagonistic activity represent promising alternatives to chemical fungicides in managing plant pathogens.The lipopeptides(LPs)iturin and fengycin derived f...Biocontrol microorganisms and their derived metabolites with antagonistic activity represent promising alternatives to chemical fungicides in managing plant pathogens.The lipopeptides(LPs)iturin and fengycin derived from Bacillus amyloliquefaciens S76-3 exhibit highly inhibitory effects against pathogenic fungi,especially Fusarium graminearum(Fg),the primary pathogen causing Fusarium head blight(FHB)in cereals.However,the specific target of iturin and fengycin in Fg and the underlying mechanism of antagonistic activity remain unclear.Here,global transcriptome sequencing,combined with both genetic and chemical approaches,demonstrates that the LPs exhibit antagonism toward Fg by binding to multiple components in the cell membrane of Fg cells,including ergosterol,phospholipids,glycosylphosphatidylinositol,and ankyrin.Lipopeptides result in cell swelling by inducing cell wall remodeling and osmotic substance glycerol synthesis mediated by cell wall integrity and high-osmolarity glycerol signaling pathways.Furthermore,we found that LPs can activate the induced systemic resistance in wheat against FHB and deoxynivalenol accumulation.Additionally,LPs were able to promote wheat growth by regulating auxin,cytokinin,and gibberellin signaling pathways while also delaying seed germination through the stimulation of abscisic acid and ethylene signaling pathways.These findings advance knowledge on the underlying mechanism of iturin and fengycin antagonistic activity and provide a new avenue for developing agricultural and clinical broad-spectrum antifungal agents and identifying plant growth regulators in the future.展开更多
Lipopeptides are recognized as a structurally diverse group of functional biopeptides.They possess multiple biological,biotechnological and therapeutic applications and are able to affect cell membrane integrity and p...Lipopeptides are recognized as a structurally diverse group of functional biopeptides.They possess multiple biological,biotechnological and therapeutic applications and are able to affect cell membrane integrity and permeability.It is widely accepted that suppressing the interaction of redooxidation is mainly aimed by inserting functional biopeptides on form alpha-helical peptides or on form antibody.Such types of structured biomaterials have great potential in promoting signal transductions to the most organelles having geometrical and spacial structures similar to endogenous liposome forms such as lysosomes,ribosomes,mitochondria and platelets..Thus,inserting radioactive trace-elements along with biopeptides is necessary in tracing the trajectory of those radioactive micelles that are destined in targeting further complicated disease and growth factor propagation.These techniques are important in determining structure-symmetry and asymmetry leading to meso-spherical crystal-packing modes or to copolymer vesiculization.The main objective of this review is to highlight and elucidate the potential role of lipopeptides in promoting signals at surface/interface of micelles along with their functionalities in repairing cellular and nuclear damages.Moreover,state-of-the-art scientific knowledge is reviewed regarding bioconjugation and structuring charged-mono-layer and/or bi-layer phospholipidic membranes in adherent to signal-biopeptides using some advanced techniques such as ultra-sound probe based polydispersity of radioactive trace-elements assisted microdialysis as micro-separating techniques in between those miscible and immiscible compounds.展开更多
Tomato bacterial wilt is an important disease caused by Ralstonia solanacearum,which is harmful to the development of tomato industry and seriously affects the yield and quality of tomato.In this study,the strain XF-8...Tomato bacterial wilt is an important disease caused by Ralstonia solanacearum,which is harmful to the development of tomato industry and seriously affects the yield and quality of tomato.In this study,the strain XF-8 with antagonism against R.solanacearum was isolated from soil and identified as Bacillus velezensis,and its control effect on tomato bacterial wilt was better than that of kasugamycin.The disease index of tomato plants treated with XF-8 was significantly reduced(P<0.05)in the pot experiment,and the control effect was 74.25%,which was higher than 45.11%of kasugamycin treatment group.The antibacterial activity of lipopeptide extract from the fermentation supernatant of strain XF-8 was further verified,and then the inhibitory rate of the substance at the concentration of 1 mg/mL was as high as 96.20%.The microscopic investigations indicated that the surface of R.solanacearum was wrinkled and deformed after treating with lipopeptide extract,and most of the bacteria were dead and rupture of the cell membrane,which leading to the cell death.Meanwhile,the active oxygen was produced and the lipopeptide extract could also significantly induced DNA injuries of R.solanacearum.All these results confirmed that the isolated strain B.velezensis exhibited excellent effect of preventing and controlling the tomato bacterial wilt.Moreover,XF-8 strain has high inhibitory effect on 10 types of pathogenic fungi,which shows broad-spectrum bacteriostasis.This study provides a theoretical basis and strain resources for the development and application of biopesticides,and broadened the potential biocontrol value of B.velezensis.展开更多
Insufficient endogenous H_(2)O_(2)for generation of hydroxyl radicals(°OH)has strikingly compromised anti-tumor benefits of ferroptosis.Herein,we develop a H_(2)O_(2)self-supplying nanoparticle based on a pH-resp...Insufficient endogenous H_(2)O_(2)for generation of hydroxyl radicals(°OH)has strikingly compromised anti-tumor benefits of ferroptosis.Herein,we develop a H_(2)O_(2)self-supplying nanoparticle based on a pH-responsive lipopeptide C_(18)-pHis_(10).Inspired by the coordinate pattern of hemoglobin binding heme,Fe^(2+)and tetrakis(4-carboxyphenyl)porphyrin(TCPP)were delicately encapsulated by formation of coordination compounds with His.Ascorbgyl palmitate(AscP)was also incorporated into the nanoparticles for gener-ation of H_(2)O_(2)by reduction^(1)0_(2)produced from TCPP,meanwhile prevented Fe^(2+)from being oxidized.The protonation of pHis in acidic endo-lysosome induced the breakage of Fe^(2+)/His/TCPP coordinate in-teractions,leading to accelerated release of payloads and the following escape to cytoplasm.Upon laser irradiation,TCPP produces excessive^(1)0_(2)followed by conversion to H_(2)O_(2)in the presence of AscP,which is further catalyzed to lethal OH by Fe^(2+)via Fenton reaction.The self-supplying H_(2)O_(2)was found to re-sult significantly higher accumulation of lipid peroxides and more effective tumor inhibition.Overall,this work sheds new a light on H_(2)O_(2)self-supplying strategy to enhance ferroptosis by taking advantage of^(1)0_(2)generated by photodynamic therapy(PDT).展开更多
Microbial lipopeptides play an important role in apoptosis induction of tumor cells.However,there is little knowledge about the relationship between apoptosis induction and membrane fatty acids.The present study focus...Microbial lipopeptides play an important role in apoptosis induction of tumor cells.However,there is little knowledge about the relationship between apoptosis induction and membrane fatty acids.The present study focused on the effects of lipopeptides produced by Bacillus subtilis HSO121 on Bcap-37 cell lines.3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl(MTT)colorimetric assay and surface tension measurements,showed that the critical micelle concentration(CMC)was a critical level for the inhibitory activity of lipopeptides on the growth of Bcap-37 cells.Under the CMC,the order of least to greatest cytotoxicity effect on cancer cell lines by lipopeptides is C13-lipopeptide<C14-lipopepitde<C15-lipopeptide.Above CMC,all lipopeptides directly exert cytolytic activity.The flow cytometric analysis and Hoechst33258 staining experiments confirmed the apoptosis of Bcap-37 cell lines induced by lipopeptides in a dose-dependent manner.This apoptosis was associated with a significant decrease of the unsaturated degree of the cellular fatty acids of Bcap-37 cell lines due to the changes in the cellular fatty acids composition induced by the lipopeptide treatment.These results indicated that disturbance of the cellular fatty acid composition of breast cancer cell lines were related to in the cell apoptosis.Furthermore,significant difference in IC50 values of tumor cells and normal cell showed that the lipopeptide exerted selective cytotoxicity on the cancer cells.Thus HSO121 lipopeptides may have potential applications as an anticancer leads.展开更多
基金support of the Lendület(Momentum)Programme of the Hungarian Academy of Sciences(Grant No.:LP2021-28)the National Research,Development and Innovation Fund of Hungary,financed under the 2018-1.2.1-NKP funding scheme(Project No.:2018-1.2.1-NKP-2018-00005)the National Research,Development and Innovation Office,NKFIH,Hungary(Grant Nos.:K131594,2020-1-1-2-PIACI-KFI_2020-00021,and TKP2021-EGA-31).
文摘The aim of the research is to increase the applicability of lipopeptides as drugs.To this end,non-ionic triblock copolymers,namely poloxamers,were applied.The physico-chemical properties of poloxamers vary depending on the length of the blocks.In our study,we experimented with different types and systematically investigated the variation of the critical micelle concentration(CMC)of poloxamers at 25 and 37°C in different media.In addition,the cytotoxicity of the different poloxamer micelles on three different cell lines was evaluated,and based on the results,Plur104,Plur123,and Plur127 were selected.Fatty acid elongated derivatives of a short antibacterial peptide(pL1),a medium-sized anticancer peptide(pCM15),and a branched-chain vaccine antigen(pATIPC)were used as lipopeptide models,and their formulations with the selected poloxamers were investigated.The solubility and homogeneity of the lipopeptides were significantly increased,and dynamic light scattering(DLS)measurements showed the formation of small particles of around 20 nm,which were well reproducible and storable.Similar homogenous micelle formation was observed after freeze-drying and reconstitution with water.The pL1 lipopeptide,formulated with the selected poloxamers,exhibited enhanced antibacterial activity with significantly reduced haemolytic side effects.The pCM15 peptide,when incorporated into poloxamer micelles,showed significantly enhanced cytotoxicity against tumor cells.Additionally,the internalization rate of poloxamer-formulated pATIPC peptide by antigen-presenting model cells exceeded that of the unformulated peptide.Our results demonstrate the potential of poloxamers as promising tools for the formulation of lipopeptides and for the optimization of their selectivity.
基金Grants from COMRA(Grant No.DY125-15-T-01 and SOA(Grant No.2010319123366025-4)National High Technology Development Project(863 Project,Grant No.2011AA10A202-2)National Key Technologies R&D Program(Grant No.2011BAE06B04)
文摘Chromatographic separation of the marine-derived bacterium Bacillus licheniformis resulted in the isolation of two new cyclic lipopeptides named ai-Cl6 surfactin （1） and ai-Cl4 surfactin （2）, together with iso-Cm5 surfactin and iso-Cl6 surfactin. The structures of the new cyclic lipopeptides were determined through extensive spectroscopic analysis. The sequences of the amino acids in cyclic nucleus were established by the ESI-MS/MS fragmentation, which provided an efficient method to detect lipopeptides from bacterium extracts without senaration
基金financially supported by National Natural Science Foundation of China(NSFC,Nos.81873921 and 51903174)Sino-German Cooperation Group Project(No.GZ1512)+2 种基金China Postdoctoral Science Foundation(No.2021M702772)Chengdu Science and Technology Program(No.2020-GH02-00007-HZ)Sichuan University Postdoctoral Interdisciplinary Innovation Startup Foundation and the Fundamental Research Funds for Central Universities(No.2021SCU12070)。
文摘The integrated lipopeptide(RVA)/gene complexes are fabricated with bi-directional regulation on tumor cells and micro-environment.After self-assembling and target coating modification,the poly(γ-glutamic acid)(γ-PGA)/RVA nano-vectors can sequentially respond to pH&redox stimuli,and guarantee efficient therapeutic gene delivery and control release of all-trans retinoic acid.The design provides a facile but promising strategy to treat refractory cancers.
基金funded by the National Key R&D Program of China(2022YFD1901300)the National Natural Science Foundation of China(31901932)+2 种基金the Agricultural Science and Technology Innovation Program of Chinese Academy of Agricultural Sciences(CAAS-ZDRW202308 and Y2022PT12)the Beijing Innovation Consortium of Agriculture Research System(BAIC04-2022)the Science and Technology Programs of the Zunyi Tobacco(2021XM03)。
文摘The multifunctional secondary metabolites known as cyclic lipopeptides(CLPs),which are produced by a large variety of bacteria,have become a key category of plant immunity elicitors.Pseudomonas-CLPs(PsCLPs)are extremely diverse in structure and biological activity.However,an understanding of CLP-plant structure–function interactions currently remains elusive.Here,we identify medpeptin,a novel CLP from Pseudomonas mediterranea that consists of 22 amino acids.Medpeptin is synthesized by a non-ribosomal peptide synthase(NRPS)gene cluster and regulated by a quorum-sensing system.Further research indicates that medpeptin does not exhibit antimicrobial activity;instead,it induces plant cell death immunity and confers resistance to bacterial infection.Comparative transcriptome analysis and virus-induced gene silencing(VIGS)reveal a set of immune signaling candidates involved in medpeptin perception.Silencing of a cell-wall leucine-rich repeat extensin protein(NbLRX3)or a receptor-like protein kinase(NbRLK25)—but not BAK1 or SGT1—compromises medpeptin-triggered cell death and resistance to pathogen infection in Nicotiana benthamiana.Our findings point to a noncanonical mechanism of CLP sensing and suggest perspectives for the development of plant disease resistance.
基金supported by the National Natural Science Foundation of China(Nos.81573311 and 82173702).
文摘Lysobacter harbors a plethora of cryptic biosynthetic gene clusters(BGCs),albeit only a limited number have been analyzed to date.In this study,we described the activation of a cryptic polyketide synthase(PKS)/nonribosomal peptide synthetase(NRPS)gene cluster(lsh)in Lysobacter sp.DSM 3655 through promoter engineering and heterologous expression in Streptomyces sp.S001.As a result of this methodology,we were able to isolate two novel linear lipopeptides,lysohexaenetides A(1)and B(2),from the recombinant strain S001-lsh.Furthermore,we proposed the biosynthetic pathway for lysohexaenetides and identified LshA as another example of entirely iterative bacterial PKSs.This study highlights the potential of heterologous expression systems in uncovering cryptic biosynthetic pathways in Lysobacter genomes,particularly in the absence of genetic manipulation tools.
基金supported in part by the National Natural Science Foundation of China(Nos.81821092 and 81701312)Beijing Municipal Science and Technology Commission(Nos.Z181100001518005 and JQ.18024)National Key Research and Development Program of China(Nos.2017YFC0803608 and 2019YFC0118604)。
文摘We describe an application of carrier protein-free strategy in constructing a fully synthetic methamphetamine(METH)vaccine that contains three components:Toll-like receptor 2 ligand,Th2 epitope,and METH hapten.The immunological evaluation in mice revealed high titers of METH-specific antibodies induced by the construct and the activation of humoral immunity that would be beneficial for neutralization and clearance of the METH molecule.Behavio ral experiments indicated that the synthetic vaccine attenuated the acquisition of METH-induced conditioned place preference and inhibited the initiation and expression of METH-induced locomotor sensitization.These results demonstrate that the lipopeptide-based vaccine has invo ked an immune response and showed the potential of preventing the rewarding and psychoactive effects of METH.
基金funded by PhD grants of ‘Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen)’ (Nos. 101529 (MD) and 121512 (BG))The Special Research Fund (BOF) of Ghent University (01J22510 (EW) and 01D38811 (SS))
文摘Lipopeptides are currently re-emerging as an interesting subgroup in the peptide research field, having historical applications as antibacterial and antifungal agents and new potential applications as antiviral, antitumor, immune-modulating and cell-penetrating compounds. However, due to their specific structure, chromatographic analysis often requires special buffer systems or the use of trifluoroacetic acid, limiting mass spectrometry detection. Therefore, we used a traditional aqueous/acetonitrile based gradient system, containing 0.1% （m/v） formic acid, to separate four pharmaceutically relevant lipopeptides （polymyxin B1, caspofungin, daptomycin and gramicidin A1）, which were selected based upon hierarchical cluster analysis （HCA） and principal component analysis （PCA）.In total, the performance of four different C18 columns, including one UPLC column, were evaluated using two parallel approaches. First, a Derringer desirability function was used, whereby six single and multiple chromatographic response values were rescaled into one overall D-value per column. Using this approach, the YMC Pack Pro C18 column was ranked as the best column for general MS-compatible lipopeptide separation. Secondly, the kinetic plot approach was used to compare the different columns at different flow rate ranges. As the optimal kinetic column performance is obtained at its maximal pressure, the length elongation factor λ（Pmax/Pexp） was used to transform the obtained experimental data （retention times and peak capacities） and construct kinetic performance limit （KPL） curves, allowing a direct visual and unbiased comparison of the selected columns, whereby the YMC Triart C18 UPLC and ACE C18 columns performed as best. Finally, differences in column performance and the （dis）advantages of both approaches are discussed.
基金financially supported by the National Natural Science Foundation of China(31771951,32072199,31801510)the Beijing Natural Science Foundation(KZ201810011016).
文摘Listeria monocytogenes is a worrisome food-borne pathogen threatening global food safety.Our previous study proved that lipopeptide brevilaterin B showed efficient antibacterial activity against L.monocytogenes by interacting with the cell membrane.This research further explored the antibacterial mechanism of brevilaterin B against L.monocytogenes at the sub-minimum inhibition concentration via transcriptomic analysis.Brevilaterin B induced growth inhibition rather than direct membrane lysis in L.monocytogenes at the minimum inhibitory concentration.Transcriptomic analysis showed 1779 difference expressed genes,including 895 up-regulated and 884 down-regulated genes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis indicated that brevilaterin B influenced multiple pathways of L.monocytogenes,including peptidoglycan biosynthesis,membrane transport(ATP-binding cassette transports,ion transport),cellular metabolism(amino acid and lipid metabolism),ATP synthesis,and activation of the stress response(quorum sensing and bacterial chemotaxis).In conclusion,brevilaterin B affects gene expression related to biosynthesis,transport and stress response pathways on the membrane of L.monocytogenes.The present work provides the first transcriptomic assessment of the antibacterial mechanism of lipopeptide brevilaterin B at the gene level.
基金supported by the National Nature1 Science Foundation of China(30170623)the National 863 Program of China(2001AA246013).
文摘MALDI-TOF-MS technology was used for identification of lipopeptide antibiotics producedby GEB3 strain, a derivative of Bacillus subtilis 168 which was transformed by lpaB3gene. The result showed GEB3 only produced lipopeptide antibiotic surfactin. The analysisby LC-MS demonstrated that GEB3 produced standard surfactin isoforms with side chainlengths of 13,14 and 15 carbon atoms. The bioactivity detection of surfactin indicatedthat the surfactin produced by GEB3 had inhibition effect on plant pathogens Rhizoctoniasolani and Pyricularia oryzae.
基金financially supported by the Key Technologies Research and Development Program of China(2011BAE06B04-16)
文摘Agricultural application studies, including field experiments and acute toxicity tests, were conducted for lipopeptides secreted by marine-derived Bacillus marinus B-9987. Benefiting from commercially available scaled-up lipopeptide purification, the sample of impurities（isolated from target lipopeptides）, raw extracted sample（purity： 9.08%）, partially purified sample（purity： 20.86%）, and highly purified sample（purity： 87.51%） were prepared from B. marinus B-9987 fermentation broth, and used in lab-scale antagonism tests, field experiments, swarming motility tests, and acute toxicity tests. Operations and conditions in field experiments were consistent with the Pesticide-Guidelines for the Field Efficacy Trials（GB/T 17980.28-2000）, and acute toxicity tests were executed according to Toxicological Test Methods of Pesticides for Registration（GB 15670-1995）. In agar diffusion tests in vitro and pot tests in vivo, all lipopeptide samples with different purities significantly inhibited Botrytis cinerea; meanwhile the sample of impurities isolated from target lipopeptides were not effective against B. cinerea. Results of lab-scale tests showed that the target lipopeptides were effective substances against B. cinerea. Thus, partially purified and raw extracted samples were used in field experiments instead of the highly purified sample for cost saving. In the field experiments against rose grey mold, biological control efficacy of 500 mg L–1 lipopeptides reached 67.53%, slightly lower than 74.05% reached by the agrochemical pyrimethanil. However, pyrimethanil severely suppressed B. marinus B-9987, whereas the lipopeptides promoted swarming motility and biocontrol efficacy of Bacillus biomass. Lipopeptides at 87.51% purity were tested for systemic acute toxicity and confirmed as low-toxicity substances. In conclusion, low-toxicity lipopeptides were potential alternatives to agrochemicals, and they also performed good promotion when combined with homologous biological control microorganism. There were 2 breakthroughs in this research：（1） marine-derived bacterial lipopeptides inhibited grey mold caused by B. cinerea in field experiments; and（2） purified bacterial lipopeptides（sample purity： 〉87.51%） were determined to be low-toxicity substances by systemic acute toxicity tests, satisfying the strict requirement of pesticide registration in China（required purity： 〉85%）. This study provides support for using extracellularBacillus-derived lipopeptides commercially similar to Bacillus-based biological control agents.
文摘The science and technology interact with the art in several ways. Biotechnological coupled with analytical approaches can play an important role in protecting and preserving cultural heritage for future generations. Many microorganisms influenced by environmental conditions are the main responsible for biological contamination in built heritage. Biocides based on chemical compounds have been used to mitigate this problem. Thus, it is vitally important to develop proper remediation actions based on environmentally innocuous alternative. Bacillus specie is emerging as an optimistic alternative for built heritage treatment due to their capacity to produce secondary metabolites with antagonistic activities against many fungal pathogens. Therefore, the intent of this work was to access a rapid evaluation of antifungal potential of bioactive metabolites produced by Bacillus strains and simultaneously their characterization using spectroscopic (NMR) and chromatographic techniques (LC-ESI-MS). The high antifungal activity obtained for Bacillus sp. active compounds produced in this study confirms the great potential to suppress biodeteriogenic fungi growth on historical artworks. Additionally, the proposed methodology allowed to access bioactive metabolites produced without need of the laborious total previous isolation and could be used as a viable alternative to be employed for screening and production of new green biocides.
基金This work was supported by the National Natural Science Foundation of China(No.50374038,50574040)Specialized Research Fund for the Doctoral Program of Higher Education(20030251002)+1 种基金Key Project of the Ministry of Education(03071)by the Department of Science and Technology Shanghai(045407017).
文摘The molar absorption coefficients of each of 14 kinds of amino acids were determined by the spectrophotometric method, and the mean molar absorption coefficients of 37 different mixtures of each with amino acid composition exactly equivalent to that of the peptide chain of the corresponding lipopeptide were determined based on calculation or experimental. The significance of the results is that the mean molar absorption coefficients strongly demonstrate the regular patterns, though different amino acids bear quite different molar absorption coefficients.
文摘This paper describes the synthesis of peptide fragments for use in a new type of combinatorial discovery technology, in which the building blocks are brought together by non-covalent interactions, rather than direct chemical bonding. The building blocks of interest—in this case different amino acids—are converted to amphiphiles by attachment to lipid tails. The amphiphiles, when mixed together in aqueous phase, are designed so that they aggregate spontaneously to form micelles. The building blocks form the headgroups of each of the amphiphiles, and these headgroups cover the surface of the micelle in a dynamic close-packed fluid mosaic array. These building blocks come together so closely that two- or three-dimensional structures are created on the surface of the micelles, and these can be screened in biological assays to find out which combination of building blocks is able to elicit a biological response. Lipopeptides consisting of two residues of lipoamino acid and other amino acids moieties have been designed, synthesized, characterized and the ability of these constructs to form supra-molecular assemblies is demonstrated.
文摘In biological controls using <em>Bacillus</em> spp., cyclic lipopeptides play a role as elicitors to induce disease resistance on various host plants. However, it is still unclear the specificity between cyclic lipopeptides and host plants to induce disease resistance. In this study, we aimed to clarify the specificity to induce disease resistance among cyclic lipopeptides on various host plants. Our data clearly showed both cyclic lipopeptides conferred disease suppression on most of host plants, but at different range of cyclic lipopeptide concentration. Our findings contribute to understanding the complex on the specificity of cyclic lipopeptide derived induced disease resistance.
基金The authors acknowledge the support of the Lendulet(Momentum)Programme of the Hungarian Academy of Sciences(Grant No.:LP2021-28)National Research,Development and Innovation Fund of Hungary(Grant Nos.:OTKA K142904,OTKA ANN 139484,KKP_22144180,TKP2021-EGA-31,and VEKOP-2.3.3-15-2016-00020)+2 种基金Marie-Skłodowska-Curie action(H2020-MSCA-ITN BactiVAX,grant agreement No.956758)CIBERES,an initiative of Instituto de Salud Carlos III(ISCIII,Madrid,Spain)Agencia Estatal Investigacion of Spain for the Severo Ochoa Center of Excellence Accreditation CEX2021-001136-S,funded by MCIN/AEI/10.13039/501100011033.
文摘In the last decade,the rise of antibiotic resistance has heightened interest in antimicrobial peptides and lipopeptides as promising alternatives to conventional antibiotics because of their lower propensity to develop resistance.However,lipopeptides often show undesired cytotoxicity due to their non-selective membrane disruptive effect,and their limited aqueous solubility represents a matter of concern from a pharmaceutical point of view.This study demonstrates a panel of ultrashort cationic lipopeptides(USCLs)consisting of a tetrapeptide(L1),originated from buforin II,coupled with saturated fatty acids of different lengths.Our results highlight that the 16-carbon fatty acid lipopeptide(Pal-L1)exhibits relevant antibacterial activity against multiresistant Staphylococcus aureus strain.However,the formation of heterogenic aggregates in cell culturemedium and toxic effects on human cells were also observed.Pal-L1 formulation with the randomly methylatedα-cyclodextrin(RAMEA)and the sulfobutylether-β-cyclodextrin(SBECD)has resulted in a production of ultralow-sized molecular dispersion systems and reduced lipopeptide toxicity without compromising its antimicrobial activity.With titration 1H-NMR,2D NMR experiments,together with molecular dynamics simulations,we described the size,structure,stoichiometry,and dissociation constant of the supramolecular complexes.Interactions of neutral and negatively chargedmodel liposomes with Pal-L1 lipopeptide in the presence or absence of cyclodextrins serve an explanation for the membrane selectivity,and based on the results,we proposed a potential mechanism of action for the Pal-L1+cyclodextrin complexes on different biological membranes.Overall,our model characterization points out that cyclodextrin formulation improves the therapeutical applicability of lipopeptides.
基金supported by grants from the National Key R&D Program of China(2022YFD1400102and 2018YFD02005)the National Natural Science Foundation of China(32272170 and 31271717)+1 种基金China Postdoctoral Science Foundation(2021M701348)Hubei Hongshan Laboratory(2022hspy010).
文摘Biocontrol microorganisms and their derived metabolites with antagonistic activity represent promising alternatives to chemical fungicides in managing plant pathogens.The lipopeptides(LPs)iturin and fengycin derived from Bacillus amyloliquefaciens S76-3 exhibit highly inhibitory effects against pathogenic fungi,especially Fusarium graminearum(Fg),the primary pathogen causing Fusarium head blight(FHB)in cereals.However,the specific target of iturin and fengycin in Fg and the underlying mechanism of antagonistic activity remain unclear.Here,global transcriptome sequencing,combined with both genetic and chemical approaches,demonstrates that the LPs exhibit antagonism toward Fg by binding to multiple components in the cell membrane of Fg cells,including ergosterol,phospholipids,glycosylphosphatidylinositol,and ankyrin.Lipopeptides result in cell swelling by inducing cell wall remodeling and osmotic substance glycerol synthesis mediated by cell wall integrity and high-osmolarity glycerol signaling pathways.Furthermore,we found that LPs can activate the induced systemic resistance in wheat against FHB and deoxynivalenol accumulation.Additionally,LPs were able to promote wheat growth by regulating auxin,cytokinin,and gibberellin signaling pathways while also delaying seed germination through the stimulation of abscisic acid and ethylene signaling pathways.These findings advance knowledge on the underlying mechanism of iturin and fengycin antagonistic activity and provide a new avenue for developing agricultural and clinical broad-spectrum antifungal agents and identifying plant growth regulators in the future.
基金The authors acknowledge the INATAA Mentouri Constantine University of Algeria,University Putra Malaysia and Malaysian Palm Oil Board for further innovation and support to researches relevant to food crystallization,isomerization and copolymerization destined for enriching emulsions food products.
文摘Lipopeptides are recognized as a structurally diverse group of functional biopeptides.They possess multiple biological,biotechnological and therapeutic applications and are able to affect cell membrane integrity and permeability.It is widely accepted that suppressing the interaction of redooxidation is mainly aimed by inserting functional biopeptides on form alpha-helical peptides or on form antibody.Such types of structured biomaterials have great potential in promoting signal transductions to the most organelles having geometrical and spacial structures similar to endogenous liposome forms such as lysosomes,ribosomes,mitochondria and platelets..Thus,inserting radioactive trace-elements along with biopeptides is necessary in tracing the trajectory of those radioactive micelles that are destined in targeting further complicated disease and growth factor propagation.These techniques are important in determining structure-symmetry and asymmetry leading to meso-spherical crystal-packing modes or to copolymer vesiculization.The main objective of this review is to highlight and elucidate the potential role of lipopeptides in promoting signals at surface/interface of micelles along with their functionalities in repairing cellular and nuclear damages.Moreover,state-of-the-art scientific knowledge is reviewed regarding bioconjugation and structuring charged-mono-layer and/or bi-layer phospholipidic membranes in adherent to signal-biopeptides using some advanced techniques such as ultra-sound probe based polydispersity of radioactive trace-elements assisted microdialysis as micro-separating techniques in between those miscible and immiscible compounds.
基金supported by the National Key R&D Program of China(grant no.2022YFD1400700)the Fujian Agriculture and Forestry University Construction Project for the Technological Innovation and Service System of the Tea Industry Chain(K1520005A03)+1 种基金The Open Funds of the State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crops,Fujian Agriculture and Forestry University(SKL2023005)The Special Fund for Scientific and Technological Innovation of Fujian Agriculture and Forestry University(KFB23012).
文摘Tomato bacterial wilt is an important disease caused by Ralstonia solanacearum,which is harmful to the development of tomato industry and seriously affects the yield and quality of tomato.In this study,the strain XF-8 with antagonism against R.solanacearum was isolated from soil and identified as Bacillus velezensis,and its control effect on tomato bacterial wilt was better than that of kasugamycin.The disease index of tomato plants treated with XF-8 was significantly reduced(P<0.05)in the pot experiment,and the control effect was 74.25%,which was higher than 45.11%of kasugamycin treatment group.The antibacterial activity of lipopeptide extract from the fermentation supernatant of strain XF-8 was further verified,and then the inhibitory rate of the substance at the concentration of 1 mg/mL was as high as 96.20%.The microscopic investigations indicated that the surface of R.solanacearum was wrinkled and deformed after treating with lipopeptide extract,and most of the bacteria were dead and rupture of the cell membrane,which leading to the cell death.Meanwhile,the active oxygen was produced and the lipopeptide extract could also significantly induced DNA injuries of R.solanacearum.All these results confirmed that the isolated strain B.velezensis exhibited excellent effect of preventing and controlling the tomato bacterial wilt.Moreover,XF-8 strain has high inhibitory effect on 10 types of pathogenic fungi,which shows broad-spectrum bacteriostasis.This study provides a theoretical basis and strain resources for the development and application of biopesticides,and broadened the potential biocontrol value of B.velezensis.
基金funding of National Natural Science Foundation of China(Nos.82304426 and 81573372)Postdoctoral Fellowship Program of CPSF(No.GZC20231730)Career Development Support Plan for Young and Middle-aged Teachers in Shenyang Pharmaceutical University(No.ZQN2014A03).
文摘Insufficient endogenous H_(2)O_(2)for generation of hydroxyl radicals(°OH)has strikingly compromised anti-tumor benefits of ferroptosis.Herein,we develop a H_(2)O_(2)self-supplying nanoparticle based on a pH-responsive lipopeptide C_(18)-pHis_(10).Inspired by the coordinate pattern of hemoglobin binding heme,Fe^(2+)and tetrakis(4-carboxyphenyl)porphyrin(TCPP)were delicately encapsulated by formation of coordination compounds with His.Ascorbgyl palmitate(AscP)was also incorporated into the nanoparticles for gener-ation of H_(2)O_(2)by reduction^(1)0_(2)produced from TCPP,meanwhile prevented Fe^(2+)from being oxidized.The protonation of pHis in acidic endo-lysosome induced the breakage of Fe^(2+)/His/TCPP coordinate in-teractions,leading to accelerated release of payloads and the following escape to cytoplasm.Upon laser irradiation,TCPP produces excessive^(1)0_(2)followed by conversion to H_(2)O_(2)in the presence of AscP,which is further catalyzed to lethal OH by Fe^(2+)via Fenton reaction.The self-supplying H_(2)O_(2)was found to re-sult significantly higher accumulation of lipid peroxides and more effective tumor inhibition.Overall,this work sheds new a light on H_(2)O_(2)self-supplying strategy to enhance ferroptosis by taking advantage of^(1)0_(2)generated by photodynamic therapy(PDT).
基金This work was supported in part by grants from the National Natural Science Foundation of China(Nos.50574040,30700015)the Ministry of Science and Technology of China(2007CB707801)+3 种基金Shanghai Science and Technology Commission(No.071607014)China Postdoctoral Science Foundation(20080440545)the National Programs for High Technology Research and Development Program(863 Program)(No.2006AA09Z402)Key Project of International Cooperation(2007DFB31620).L.Z.is an awardee for Hundred Talents Program.
文摘Microbial lipopeptides play an important role in apoptosis induction of tumor cells.However,there is little knowledge about the relationship between apoptosis induction and membrane fatty acids.The present study focused on the effects of lipopeptides produced by Bacillus subtilis HSO121 on Bcap-37 cell lines.3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl(MTT)colorimetric assay and surface tension measurements,showed that the critical micelle concentration(CMC)was a critical level for the inhibitory activity of lipopeptides on the growth of Bcap-37 cells.Under the CMC,the order of least to greatest cytotoxicity effect on cancer cell lines by lipopeptides is C13-lipopeptide<C14-lipopepitde<C15-lipopeptide.Above CMC,all lipopeptides directly exert cytolytic activity.The flow cytometric analysis and Hoechst33258 staining experiments confirmed the apoptosis of Bcap-37 cell lines induced by lipopeptides in a dose-dependent manner.This apoptosis was associated with a significant decrease of the unsaturated degree of the cellular fatty acids of Bcap-37 cell lines due to the changes in the cellular fatty acids composition induced by the lipopeptide treatment.These results indicated that disturbance of the cellular fatty acid composition of breast cancer cell lines were related to in the cell apoptosis.Furthermore,significant difference in IC50 values of tumor cells and normal cell showed that the lipopeptide exerted selective cytotoxicity on the cancer cells.Thus HSO121 lipopeptides may have potential applications as an anticancer leads.
