Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety...Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future,aiming to provide valuable insights and references for the continued advancement of peptidebased drugs.展开更多
BACKGROUND Malnutrition is common in critically ill patients,and it is associated with an increased risk of complications.Early enteral nutrition with adequate caloric and protein intake is critical nevertheless it is...BACKGROUND Malnutrition is common in critically ill patients,and it is associated with an increased risk of complications.Early enteral nutrition with adequate caloric and protein intake is critical nevertheless it is difficult to achieve.Peptide-based formulas have been shown to be beneficial in patients with feeding intolerance.However,there are limited studies showing the efficacy and safety of high-protein peptide-based formula in critically ill surgical patients.AIM To determine the effects of a high-protein peptide formulation on gastrointestinal tolerance,nutritional status,biochemical changes,and adverse events in patients in the surgery intensive care unit(SICU)compared to an isocaloric isonitrogenous standard polymeric formulation.METHODS This study was a multi-center double-blind,randomized controlled trial.We enrolled adult patients in the surgical intensive care unit,age≥15 years and expected to receive enteral feeding for at least 5-14 d post-operation.They were randomly assigned to receive either the high-protein peptide-based formula or the isocaloric isonitrogenous standard formula for 14 d.Gastric residual volume(GRV),nutritional status,body composition and biochemical parameters were assessed at baseline and on days 3,5,7,9,11,and 14.RESULTS A total of 19 patients were enrolled,9 patients in the peptide-based formula group and 10 patients in the standard formula group.During the study period,there were no differences of the average GRV,body weight,body composition,nutritional status and biochemical parameters in the patients receiving peptide-based formula,compared to the standard regimen.However,participants in the standard formula lost their body weight,body mass index(BMI)and skeletal muscle mass significantly.While body weight,BMI and muscle mass were maintained in the peptide-based formula,from baseline to day 14.Moreover,the participants in the peptide-based formula tended to reach their caloric target faster than the standard formula.CONCLUSION The study emphasizes the importance of early nutritional support in the SICU and showed the efficacy and safety of a high-protein,peptide-based formula in meeting caloric and protein intake targets while maintaining body weight and muscle mass.展开更多
Peptide-based probes play prominent roles in biomedical research due to their promising properties such as high biocompatibility,fast excretion, favorable pharmacokinetics as well as easy and robust preparation. Consi...Peptide-based probes play prominent roles in biomedical research due to their promising properties such as high biocompatibility,fast excretion, favorable pharmacokinetics as well as easy and robust preparation. Considering the translation of imaging probes into clinical applications, peptide-based probes remain to be the most desirable and optimal candidates. This review summarized the development of peptide-based probes with promising imaging modalities and highlighted the successful applications for in vivo biomedical imaging.展开更多
Herein,we utilized nucleic acids induced peptide co-assembly strategy to develop novel nucleic acids induced peptide-based AIE(NIP-AIE)nanoparticles.Strong fluorescent of AIE could be observed when a little amount of ...Herein,we utilized nucleic acids induced peptide co-assembly strategy to develop novel nucleic acids induced peptide-based AIE(NIP-AIE)nanoparticles.Strong fluorescent of AIE could be observed when a little amount of nucleic acids was added into the peptide solution,and the intensity could be regulated by the concentration of nucleic acids.This AIE nanoparticle with good biocompatibility could achieve fast cell imaging.It is also proved that the fluorescence intensity of AIE decreased with time,which indicates that the reducible cross-linkers of Wpc peptide by GSH and nanoparticles gradually disintegrate in cell.Based on the different of AIE fluorescence signals which regulated by the formation and disintegration of nanoparticles,this AIE system is expected to be used for real-time monitoring of drug release from peptide-based nano carriers in vivo or in vitro,and may provide a new platform for the construction of other organic AIE nanoparticles.展开更多
Peptide-based vaccines only contain peptide epitopes and exclude unnecessary biological materials,which greatly reduces the risk of causing an undesired immune response and further improves the safety profile,garnerin...Peptide-based vaccines only contain peptide epitopes and exclude unnecessary biological materials,which greatly reduces the risk of causing an undesired immune response and further improves the safety profile,garnering considerable interest in vaccine development.However,the immunogenicity induced by these peptides alone is not potent enough to elicit an effective immune response.Recently,combining the adjuvants with peptide antigens has shown promising effects to realize a satisfying immune response.In this review,we discuss the development of immunoadjuvants to enhance the safety and efficacy of peptide-based vaccines.The emphasis is placed on the application and clinical translation of nanotechnology-based adjuvants,highlighting the associated challenges and exploring future directions.展开更多
Peptide-based materials that have diverse structures and functionalities are an important type of biomaterials.In former times,peptide-based nanomaterials with excellent stability were constructed through self-assembl...Peptide-based materials that have diverse structures and functionalities are an important type of biomaterials.In former times,peptide-based nanomaterials with excellent stability were constructed through self-assembly.Compared with individual peptides,peptide-based self-assembly nanomaterials that form well-ordered superstructures possess many advantages such as good thermo-and mechanical stability,semiconductivity,piezoelectricity and optical properties.Moreover,due to their excellent biocompatibility and biological activity,peptide-based self-assembly nanomaterials have been vastly used in different fields.In this review,we provide the advances of peptide-based self-assembly nanostructures,focusing on the driving forces that dominate peptide self-assembly and assembly mechanisms of peptides.After that,we outline the synthesis and properties of peptide-based nanomaterials,followed by the applications of functional peptide nanomaterials.Finally,we provide perspectives on the challenges and future of peptide-based nanomaterials.展开更多
Hydrogels are a class of special materials that contain a large amount of water and behave like rubber.These materials have found broad applications in tissue engineering,cell culturing,regenerative medicine etc.Recen...Hydrogels are a class of special materials that contain a large amount of water and behave like rubber.These materials have found broad applications in tissue engineering,cell culturing,regenerative medicine etc.Recently,the exploration of peptide-based supramolecular hydrogels has greatly expanded the repertoire of hydrogels suitable for biomedical applications.However,the mechanical properties of peptide-based hydrogels are intrinsically weak.Therefore,it is crucial to develop methods that can improve the mechanical stability of such peptide-based hydrogels.In this review,we explore the factors that determine or influence the mechanical stability of peptide-based hydrogels and summarize several key elements that may guide scientists to achieve mechanically improved hydrogels.In addition,we exemplified several methods that have been successfully developed to prepare hydrogels with enhanced mechanical stability.These mechanically strong peptide-based hydrogels may find broad applications as novel biomaterials.It is still challenging to engineer hydrogels in order to mimic the mechanical properties of biological tissues.More hydrogel materials with optimal mechanical properties suitable for various types of biological applications will be available in the near future.展开更多
Traditional surgical treatment is difficult to thoroughly remove esophageal squamous cell carcinomas(ESCC),postoperative recurrence caused by residual tumor cells is a critical factor in the poor prognosis.Since surgi...Traditional surgical treatment is difficult to thoroughly remove esophageal squamous cell carcinomas(ESCC),postoperative recurrence caused by residual tumor cells is a critical factor in the poor prognosis.Since surgical resection promotes the local angiogenesis at the tumor site,further exacerbating the proliferation and invasion of residual tumor cells,it is urgent to inhibit angiogenesis after surgery.Here,a functional peptide-based nanomedicine was obtained from peptide–drug conjugates,which are composed of a hydrophilic targeting motif(vascular endothelial growth factor family and their receptors(VEGFR)targeting peptide for anti-angiogenesis),an ester-linked hydrophobic oridonin(ORI).The nanomedicine exhibits esterase-catalyzed disassembly and drug release,significantly enhanced the anti-tumor efficacy of chemotherapeutics in a postoperative tumor recurrence model through synergistic anti-angiogenic strategies.This study provides an integrated solution for anti-angiogenesisaugmented chemotherapy and demonstrates the encouraging potential for postoperative treatment.展开更多
Natural endogenous materials(NEMs),such as cell and cell derivatives,polysaccharide,protein and peptide,and nucleic acid-derived vectors,often exhibit biocompatibility,biodegradability and natural homing ability,which...Natural endogenous materials(NEMs),such as cell and cell derivatives,polysaccharide,protein and peptide,and nucleic acid-derived vectors,often exhibit biocompatibility,biodegradability and natural homing ability,which can minimize adverse reactions in vivo and have the potential to improve drug delivery efficacy.Currently,a variety of drug delivery systems(DDSs)based on NEMs have been constructed for macromolecules to address the challenges posed by their inherent large size,intricate structure,low permeability,and susceptibility to harsh environments.The aim of this article is to provide a comprehensive overview of various delivery strategies that predominantly utilize NEMs as carriers for macromolecular delivery.By thoroughly discussing the pros and cons of NEM-based DDSs,we hope to provide valuable insights into future innovations in pharmaceutical science,with a focus on improving therapeutic outcomes through advanced drug formulations.展开更多
The World Health Organization has declared the rapidly spreading coronavirus to be a global pandemic.The FDA is yet to approve a vaccine for human novel coronavirus.Here,we developed a peptide-based vaccine and used h...The World Health Organization has declared the rapidly spreading coronavirus to be a global pandemic.The FDA is yet to approve a vaccine for human novel coronavirus.Here,we developed a peptide-based vaccine and used high-throughput screening by molecular dynamics simulation to identify T-cell-and p-cell-recognized epitopes for producing specific antibod-ies against SARS-nCoV-2.We construct~12 P'antigenic epitope peptides to develop a more effective vaccine and identify specific antibodies.These epitope peptides selectively presented the best antigen presentation scores for both human pMHC class I and II alleles to develop a strong binding affinity.All antigens identified of SARS-nCoV-2 different proteins by each attached specific~1-7 L linker adaptor were used to construct a broad single peripheral peptide vaccine.It is expected to be highly antigenic with a minimum allergic effect.As a result of these exciting outcomes,expressing a vaccine using the intimated peptide was highly promising and positive to be highly proposed as epitope-based peptide vaccine of specific antibody against SARS-nCoV-2 by initiating T cells and β-cells.An in vitro study for the proposed peptide-based vaccine is.mostly recommended.Further clinical trials are required to check the efficacy of this vaccine.展开更多
Lysine acetylation is one of the most prevalent and important posttranslational modifications(PTMs) in proteins. The process can be recognized by bromodomains(BRDs), which are a class of proteininteraction modules inv...Lysine acetylation is one of the most prevalent and important posttranslational modifications(PTMs) in proteins. The process can be recognized by bromodomains(BRDs), which are a class of proteininteraction modules involved in chromatin remodeling and transcriptional activation. The development of BRD fluorescent probes will be useful for monitoring the activity of BRDs in living cells as well as aiding inhibitor development. Herein we designed a peptide-based probe based on the proximity-induced protein conjugation reaction. The peptide-based probe is capable of covalently and selectively reacting with the unique cysteine residue in the bromodomain through proximity effect. Our experimental data showed that the probe displayed noticeable fluorescence response upon addition of BRD4(1). In-gel fluorescence scanning demonstrated that BRD4(1) can be covalently labelled by the probe. Moreover, the probe was shown to selectively detect BRD4(1) over other proteins. We envision that the probe developed in this study will provide a useful tool to further investigate the biological roles of BRDs.展开更多
The binding energies of thirty-six hydrogen-bonded peptide-base complexes, including the peptide backbone-ase complexes and amino acid side chain-base complexes, are evaluated using the analytic potential energy funct...The binding energies of thirty-six hydrogen-bonded peptide-base complexes, including the peptide backbone-ase complexes and amino acid side chain-base complexes, are evaluated using the analytic potential energy function established in our lab recently and compared with those obtained from MP2, AMBER99, OPLSAA/L, and CHARMM27 calculations. The comparison indicates that the analytic potential energy function yields the binding energies for these complexes as reasonable as MP2 does, much better than the force fields do. The individual N H…O=C, N H…N, C H…O=C, and C H…N attractive interaction energies and C=O…O=C, N H…H N, C H…H N, and C H…H C repulsive interaction energies, which cannot be easily obtained from ab initio calculations, are calculated using the dipole-dipole interaction term of the analytic potential energy function. The individual N H…O=C, C H…O=C, C H…N attractive interactions are about 5.3±1.8, 1.2±0.4, and 0.8 kcal/mol, respectively, the individual N H … N could be as strong as about 8.1 kcal/mol or as weak as 1.0 kcal/mol, while the individual C=O…O=C, N H…H N, C H…H N, and C H…H C repulsive interactions are about 1.8±1.1, 1.7±0.6, 0.6±0.3, and 0.35±0.15 kcal/mol. These data are helpful for the rational design of new strategies for molecular recognition or supramolecular assemblies.展开更多
Due to low immobilized ligand density,limited binding capacity,and severe interference from serum proteins,developing ideal peptide-based biomaterials for precise recognition and in vivo analysis of biopharmaceuticals...Due to low immobilized ligand density,limited binding capacity,and severe interference from serum proteins,developing ideal peptide-based biomaterials for precise recognition and in vivo analysis of biopharmaceuticals remains a huge challenge.In this study,mimotope peptide modified pompon mum-like biomimetic magnetic microparticles(MMPs,3.8μm)that mimic the specific functionalities of CD20 on malignant B cells were developed for the first time.Benefit from the numerous ligand binding sites(Ni^(2+))on the pompon mum-like MMPs,these novel materials achieved≥10 times higher peptide ligand densities(>2300 mg/g)and antibody binding capacities(1380 mg/g)compared to previous reported biomaterials.Leveraging the high specificity of the mimotope peptide,rituximab can be precisely recognized and enriched from cell culture media or serum samples.We also established an LC-MS/MS method using the MMPs for tracking rituximab biotransformation in patient serum.Intriguingly,deamidation of Asn55 and Asn33,as well as oxidation of Met81 and Met34 were observed at the key complementarity determining regions of rituximab,which could potentially influence antibody function and require careful monitoring.Overall,these versatile biomimetic MMPs demonstrate superior recognition and enrichment capabilities for target antibodies,offering interesting possibilities for biotransformation analysis of biopharmaceuticals in patient serum.展开更多
Objectives:Cronobacter sakazakii,formerly Enterobacter sakazakii,is an emerging ubiquitous and opportunistic foodborne pathogen with a high mortality rate.It has been implicated in cases of meningitis,septicaemia,and ...Objectives:Cronobacter sakazakii,formerly Enterobacter sakazakii,is an emerging ubiquitous and opportunistic foodborne pathogen with a high mortality rate.It has been implicated in cases of meningitis,septicaemia,and necrotizing enterocolitis among infants worldwide in association with powdered infant formula(PIF).This study was an insilico designed peptide base kit framework,using immunoinformatic techniques for quick detection of C.sakazakii in PIF.Materials and Methods:In the present study,a peptide-based kit was designed with a bioinformatic technique to rapidly identify C.sakazakii in PIF using fhE,secY,and bcsC,which are genes responsible for its bioflm formation,as target genes.The antigenicity,membrane topology,and the presence of signal peptides of the target genes were analysed using VaxiJen,DeepTMHMM,and SignalP servers.To provide stability and fexibility to the multiple-epitope construct,the linear B cells and helper T cells(IL-4(interleukin 4)and IL-10(interleukin 10)inducing epitopes)were linked with a GSGSG linker followed by the addition of protein disulphide bonds.To ascertain specifcity,the multi-epitope construct was molecularly docked against genes from sources other than PIF,like alfalfa,and the environment,with PIF being the highest:–328.48.Finally,the codons were modifed using the pET28a(+)vector,and the resultant multi-epitope construct was successfully cloned in silico.Results:The fnal construct had a length of 486 bp,an instability index of 23.26,a theoretical pI of 9.34,a molecular weight of 16.5 kDa,and a Z-score of–3.41.Conclusions:The multi-epitope peptide construct could be a conceptual framework for creating a C.sakazakii peptide-based detection kit,which has the potential to provide fast and effcient detection.However,there is a need for additional validation through the in vitro and in vivo techniques.展开更多
Atherosclerosis is a severe cardiovascular disease followed by the accumulation of atherosclerotic plaques within the lumen of blood vessels resulting in reduced blood flow thus initiating a series of events.Conventio...Atherosclerosis is a severe cardiovascular disease followed by the accumulation of atherosclerotic plaques within the lumen of blood vessels resulting in reduced blood flow thus initiating a series of events.Conventional therapies for atherosclerosis encounter multiple chal-lenges,especially difficulty in precisely concentrating in certain affected regions and the potential for unwanted side effects.Consequently,scientists are focused on developing nanoformulations for atherosclerosis diagnosis and therapy.Peptide-based nanomedi-cines improve conventional therapies by offering improved structural and therapeutic stability and enabling target-specific delivery.Their inherent biocompatibility and biodegradability additionally render them desirable materials intended for in vivo use.This review manu-script aims to provide an in-depth overview of peptide-based nano-medicines for atherosclerosis,focusing on targeted cells like endothelial cells,macrophages,and monocytes and their interaction with different plaque components.Moreover,the manuscript also highlights the latest progress in multimodal techniques and provides a comprehensive overview of limitations associated with their practical implementation.展开更多
The substantial economic impact of non-healing wounds,scarring,and burns stemming from skin injuries is evident,resulting in a financial burden on both patients and the healthcare system.This review paper provides an ...The substantial economic impact of non-healing wounds,scarring,and burns stemming from skin injuries is evident,resulting in a financial burden on both patients and the healthcare system.This review paper provides an overview of the skin’s vital role in guarding against various environmental challenges as the body’s largest protective organ and associated developments in biomaterials for wound healing.We first introduce the composition of skin tissue and the intricate processes of wound healing,with special attention to the crucial role of immunomodulation in both acute and chronic wounds.This highlights how the imbalance in the immune response,particularly in chronic wounds associated with underlying health conditions such as diabetes and immunosuppression,hinders normal healing stages.Then,this review distinguishes between traditional wound-healing strategies that create an optimal microenvironment and recent peptide-based biomaterials that modulate cellular processes and immune responses to facilitate wound closure.Additionally,we highlight the importance of considering the stages of wounds in the healing process.By integrating advanced materials engineering with an in-depth understanding of wound biology,this approach holds promise for reshaping the field of wound management and ultimately offering improved outcomes for patients with acute and chronic wounds.展开更多
基金supported by the National Natural Science Foundation of China (Nos. 82173674 and 82204195)。
文摘Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future,aiming to provide valuable insights and references for the continued advancement of peptidebased drugs.
文摘BACKGROUND Malnutrition is common in critically ill patients,and it is associated with an increased risk of complications.Early enteral nutrition with adequate caloric and protein intake is critical nevertheless it is difficult to achieve.Peptide-based formulas have been shown to be beneficial in patients with feeding intolerance.However,there are limited studies showing the efficacy and safety of high-protein peptide-based formula in critically ill surgical patients.AIM To determine the effects of a high-protein peptide formulation on gastrointestinal tolerance,nutritional status,biochemical changes,and adverse events in patients in the surgery intensive care unit(SICU)compared to an isocaloric isonitrogenous standard polymeric formulation.METHODS This study was a multi-center double-blind,randomized controlled trial.We enrolled adult patients in the surgical intensive care unit,age≥15 years and expected to receive enteral feeding for at least 5-14 d post-operation.They were randomly assigned to receive either the high-protein peptide-based formula or the isocaloric isonitrogenous standard formula for 14 d.Gastric residual volume(GRV),nutritional status,body composition and biochemical parameters were assessed at baseline and on days 3,5,7,9,11,and 14.RESULTS A total of 19 patients were enrolled,9 patients in the peptide-based formula group and 10 patients in the standard formula group.During the study period,there were no differences of the average GRV,body weight,body composition,nutritional status and biochemical parameters in the patients receiving peptide-based formula,compared to the standard regimen.However,participants in the standard formula lost their body weight,body mass index(BMI)and skeletal muscle mass significantly.While body weight,BMI and muscle mass were maintained in the peptide-based formula,from baseline to day 14.Moreover,the participants in the peptide-based formula tended to reach their caloric target faster than the standard formula.CONCLUSION The study emphasizes the importance of early nutritional support in the SICU and showed the efficacy and safety of a high-protein,peptide-based formula in meeting caloric and protein intake targets while maintaining body weight and muscle mass.
基金partially supported by grants from the National Natural Science Foundation of China(NSFC Nos. 21708012,81773674, 81573383,21390402, 81725009, 21788102, 81425015)111 Project (No. B17019)+6 种基金NKR&DPC (No. 2016YFA00900)NSFHP(Nos. 2017CFB151, 2017CFA024, 2017CFB711, 2016ACA126)ABRPSTCS (No. SYG201521)NSFJP (No. BK20160387)Shenzhen Science and Technology Research Grant (No. JCYJ20170303170809222)self-determined research funds of CCNU from the colleges, basic research and operation of MOE for the Central Universities (No. 23020205170469)Wuhan Morning Light Plan of Youth Science and Technology (No. 201705304010321)
文摘Peptide-based probes play prominent roles in biomedical research due to their promising properties such as high biocompatibility,fast excretion, favorable pharmacokinetics as well as easy and robust preparation. Considering the translation of imaging probes into clinical applications, peptide-based probes remain to be the most desirable and optimal candidates. This review summarized the development of peptide-based probes with promising imaging modalities and highlighted the successful applications for in vivo biomedical imaging.
基金financial support from the Natural Science Foundation of China(Nos.21778009,21977010 and 81701818)the Natural Science Foundation of Guangdong Province(No.2020A1515010522)+4 种基金the Guangdong Foundation for Basic and Applied Basic Research(No.2019A1515110365)the Shenzhen Science and Technology Innovation Committee(Nos.JCYJ20180507181527112,JCYJ201805081522131455 and JCYJ20170817172023838)the China Postdoctoral Science Foundation(No.2020M670054)financial support from Beijing National Laboratory of Molecular Science open grant(No.BNLMS20160112)Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions(No.2019SHIBS0004)。
文摘Herein,we utilized nucleic acids induced peptide co-assembly strategy to develop novel nucleic acids induced peptide-based AIE(NIP-AIE)nanoparticles.Strong fluorescent of AIE could be observed when a little amount of nucleic acids was added into the peptide solution,and the intensity could be regulated by the concentration of nucleic acids.This AIE nanoparticle with good biocompatibility could achieve fast cell imaging.It is also proved that the fluorescence intensity of AIE decreased with time,which indicates that the reducible cross-linkers of Wpc peptide by GSH and nanoparticles gradually disintegrate in cell.Based on the different of AIE fluorescence signals which regulated by the formation and disintegration of nanoparticles,this AIE system is expected to be used for real-time monitoring of drug release from peptide-based nano carriers in vivo or in vitro,and may provide a new platform for the construction of other organic AIE nanoparticles.
基金supported in part by Startup and Retention Funds from the R.Ken Coit College of Pharmacy at The University of Arizona(UArizona)a PhRMA Foundation Faculty Starter Grant in Drug Delivery,UArizona Comprehensive Cancer Center(UACCC)Internal Pilot Awardthe National Institutes of Health(NIH)grants(Nos.R35GM147002 and R01CA272487).
文摘Peptide-based vaccines only contain peptide epitopes and exclude unnecessary biological materials,which greatly reduces the risk of causing an undesired immune response and further improves the safety profile,garnering considerable interest in vaccine development.However,the immunogenicity induced by these peptides alone is not potent enough to elicit an effective immune response.Recently,combining the adjuvants with peptide antigens has shown promising effects to realize a satisfying immune response.In this review,we discuss the development of immunoadjuvants to enhance the safety and efficacy of peptide-based vaccines.The emphasis is placed on the application and clinical translation of nanotechnology-based adjuvants,highlighting the associated challenges and exploring future directions.
基金supported by Beijing Natural Science Foundation(JQ20038)the National Natural Science Foundation of China(61875015,T2125003,and 21801019)+1 种基金JSPS KAKENHI(Grant No.21H02873)JSPS International Joint Research Program(JPJSBP120207203).
文摘Peptide-based materials that have diverse structures and functionalities are an important type of biomaterials.In former times,peptide-based nanomaterials with excellent stability were constructed through self-assembly.Compared with individual peptides,peptide-based self-assembly nanomaterials that form well-ordered superstructures possess many advantages such as good thermo-and mechanical stability,semiconductivity,piezoelectricity and optical properties.Moreover,due to their excellent biocompatibility and biological activity,peptide-based self-assembly nanomaterials have been vastly used in different fields.In this review,we provide the advances of peptide-based self-assembly nanostructures,focusing on the driving forces that dominate peptide self-assembly and assembly mechanisms of peptides.After that,we outline the synthesis and properties of peptide-based nanomaterials,followed by the applications of functional peptide nanomaterials.Finally,we provide perspectives on the challenges and future of peptide-based nanomaterials.
基金supported by the National Natural Science Foundation of China(Grant Nos.11304156,11334004,91127026,31170813 and 11074115)China Postdoctoral Science Foundation(Grant No.2013M531312)+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutionsthe Program for New Century Excellent Talents in University
文摘Hydrogels are a class of special materials that contain a large amount of water and behave like rubber.These materials have found broad applications in tissue engineering,cell culturing,regenerative medicine etc.Recently,the exploration of peptide-based supramolecular hydrogels has greatly expanded the repertoire of hydrogels suitable for biomedical applications.However,the mechanical properties of peptide-based hydrogels are intrinsically weak.Therefore,it is crucial to develop methods that can improve the mechanical stability of such peptide-based hydrogels.In this review,we explore the factors that determine or influence the mechanical stability of peptide-based hydrogels and summarize several key elements that may guide scientists to achieve mechanically improved hydrogels.In addition,we exemplified several methods that have been successfully developed to prepare hydrogels with enhanced mechanical stability.These mechanically strong peptide-based hydrogels may find broad applications as novel biomaterials.It is still challenging to engineer hydrogels in order to mimic the mechanical properties of biological tissues.More hydrogel materials with optimal mechanical properties suitable for various types of biological applications will be available in the near future.
基金the National Natural Science Foundation of China(Nos.32000998 and U2004123)the Young Elite Scientists Sponsorship Program by Henan Association for Science and Technology(No.2022HYTP046)the China Postdoctoral Science Foundation(Nos.2019TQ0285,2019M662513,2021TQ0298,and 2022TQ0296).
文摘Traditional surgical treatment is difficult to thoroughly remove esophageal squamous cell carcinomas(ESCC),postoperative recurrence caused by residual tumor cells is a critical factor in the poor prognosis.Since surgical resection promotes the local angiogenesis at the tumor site,further exacerbating the proliferation and invasion of residual tumor cells,it is urgent to inhibit angiogenesis after surgery.Here,a functional peptide-based nanomedicine was obtained from peptide–drug conjugates,which are composed of a hydrophilic targeting motif(vascular endothelial growth factor family and their receptors(VEGFR)targeting peptide for anti-angiogenesis),an ester-linked hydrophobic oridonin(ORI).The nanomedicine exhibits esterase-catalyzed disassembly and drug release,significantly enhanced the anti-tumor efficacy of chemotherapeutics in a postoperative tumor recurrence model through synergistic anti-angiogenic strategies.This study provides an integrated solution for anti-angiogenesisaugmented chemotherapy and demonstrates the encouraging potential for postoperative treatment.
基金supported by the National Natural Science Foundation of China(No.82273884)。
文摘Natural endogenous materials(NEMs),such as cell and cell derivatives,polysaccharide,protein and peptide,and nucleic acid-derived vectors,often exhibit biocompatibility,biodegradability and natural homing ability,which can minimize adverse reactions in vivo and have the potential to improve drug delivery efficacy.Currently,a variety of drug delivery systems(DDSs)based on NEMs have been constructed for macromolecules to address the challenges posed by their inherent large size,intricate structure,low permeability,and susceptibility to harsh environments.The aim of this article is to provide a comprehensive overview of various delivery strategies that predominantly utilize NEMs as carriers for macromolecular delivery.By thoroughly discussing the pros and cons of NEM-based DDSs,we hope to provide valuable insights into future innovations in pharmaceutical science,with a focus on improving therapeutic outcomes through advanced drug formulations.
文摘The World Health Organization has declared the rapidly spreading coronavirus to be a global pandemic.The FDA is yet to approve a vaccine for human novel coronavirus.Here,we developed a peptide-based vaccine and used high-throughput screening by molecular dynamics simulation to identify T-cell-and p-cell-recognized epitopes for producing specific antibod-ies against SARS-nCoV-2.We construct~12 P'antigenic epitope peptides to develop a more effective vaccine and identify specific antibodies.These epitope peptides selectively presented the best antigen presentation scores for both human pMHC class I and II alleles to develop a strong binding affinity.All antigens identified of SARS-nCoV-2 different proteins by each attached specific~1-7 L linker adaptor were used to construct a broad single peripheral peptide vaccine.It is expected to be highly antigenic with a minimum allergic effect.As a result of these exciting outcomes,expressing a vaccine using the intimated peptide was highly promising and positive to be highly proposed as epitope-based peptide vaccine of specific antibody against SARS-nCoV-2 by initiating T cells and β-cells.An in vitro study for the proposed peptide-based vaccine is.mostly recommended.Further clinical trials are required to check the efficacy of this vaccine.
基金the financial support from the National Natural Science Foundation of China (No. 21572190)the Hong Kong Early Career Scheme Grant (No. 21300714)the City University of Hong Kong Grant (No. 9667147)
文摘Lysine acetylation is one of the most prevalent and important posttranslational modifications(PTMs) in proteins. The process can be recognized by bromodomains(BRDs), which are a class of proteininteraction modules involved in chromatin remodeling and transcriptional activation. The development of BRD fluorescent probes will be useful for monitoring the activity of BRDs in living cells as well as aiding inhibitor development. Herein we designed a peptide-based probe based on the proximity-induced protein conjugation reaction. The peptide-based probe is capable of covalently and selectively reacting with the unique cysteine residue in the bromodomain through proximity effect. Our experimental data showed that the probe displayed noticeable fluorescence response upon addition of BRD4(1). In-gel fluorescence scanning demonstrated that BRD4(1) can be covalently labelled by the probe. Moreover, the probe was shown to selectively detect BRD4(1) over other proteins. We envision that the probe developed in this study will provide a useful tool to further investigate the biological roles of BRDs.
基金supported by the National Natural Science Foundation of China(20973088,21173109,21133005)the Specialized Research Fund for the Doctoral Program of Higher Education(20102136110001)
文摘The binding energies of thirty-six hydrogen-bonded peptide-base complexes, including the peptide backbone-ase complexes and amino acid side chain-base complexes, are evaluated using the analytic potential energy function established in our lab recently and compared with those obtained from MP2, AMBER99, OPLSAA/L, and CHARMM27 calculations. The comparison indicates that the analytic potential energy function yields the binding energies for these complexes as reasonable as MP2 does, much better than the force fields do. The individual N H…O=C, N H…N, C H…O=C, and C H…N attractive interaction energies and C=O…O=C, N H…H N, C H…H N, and C H…H C repulsive interaction energies, which cannot be easily obtained from ab initio calculations, are calculated using the dipole-dipole interaction term of the analytic potential energy function. The individual N H…O=C, C H…O=C, C H…N attractive interactions are about 5.3±1.8, 1.2±0.4, and 0.8 kcal/mol, respectively, the individual N H … N could be as strong as about 8.1 kcal/mol or as weak as 1.0 kcal/mol, while the individual C=O…O=C, N H…H N, C H…H N, and C H…H C repulsive interactions are about 1.8±1.1, 1.7±0.6, 0.6±0.3, and 0.35±0.15 kcal/mol. These data are helpful for the rational design of new strategies for molecular recognition or supramolecular assemblies.
基金supported by the National Natural Science Foundation of China(82173773,82273893,82373829)the Natural Science Foundation of Guangdong Province,China(2021A0505030039,2021A0505020014)+1 种基金the High-End Foreign Experts Project,China(G2021199005L)the Science and Technology Program of Guangdong Provincial Medical Products Administration,China(2023TDZ11)。
文摘Due to low immobilized ligand density,limited binding capacity,and severe interference from serum proteins,developing ideal peptide-based biomaterials for precise recognition and in vivo analysis of biopharmaceuticals remains a huge challenge.In this study,mimotope peptide modified pompon mum-like biomimetic magnetic microparticles(MMPs,3.8μm)that mimic the specific functionalities of CD20 on malignant B cells were developed for the first time.Benefit from the numerous ligand binding sites(Ni^(2+))on the pompon mum-like MMPs,these novel materials achieved≥10 times higher peptide ligand densities(>2300 mg/g)and antibody binding capacities(1380 mg/g)compared to previous reported biomaterials.Leveraging the high specificity of the mimotope peptide,rituximab can be precisely recognized and enriched from cell culture media or serum samples.We also established an LC-MS/MS method using the MMPs for tracking rituximab biotransformation in patient serum.Intriguingly,deamidation of Asn55 and Asn33,as well as oxidation of Met81 and Met34 were observed at the key complementarity determining regions of rituximab,which could potentially influence antibody function and require careful monitoring.Overall,these versatile biomimetic MMPs demonstrate superior recognition and enrichment capabilities for target antibodies,offering interesting possibilities for biotransformation analysis of biopharmaceuticals in patient serum.
文摘Objectives:Cronobacter sakazakii,formerly Enterobacter sakazakii,is an emerging ubiquitous and opportunistic foodborne pathogen with a high mortality rate.It has been implicated in cases of meningitis,septicaemia,and necrotizing enterocolitis among infants worldwide in association with powdered infant formula(PIF).This study was an insilico designed peptide base kit framework,using immunoinformatic techniques for quick detection of C.sakazakii in PIF.Materials and Methods:In the present study,a peptide-based kit was designed with a bioinformatic technique to rapidly identify C.sakazakii in PIF using fhE,secY,and bcsC,which are genes responsible for its bioflm formation,as target genes.The antigenicity,membrane topology,and the presence of signal peptides of the target genes were analysed using VaxiJen,DeepTMHMM,and SignalP servers.To provide stability and fexibility to the multiple-epitope construct,the linear B cells and helper T cells(IL-4(interleukin 4)and IL-10(interleukin 10)inducing epitopes)were linked with a GSGSG linker followed by the addition of protein disulphide bonds.To ascertain specifcity,the multi-epitope construct was molecularly docked against genes from sources other than PIF,like alfalfa,and the environment,with PIF being the highest:–328.48.Finally,the codons were modifed using the pET28a(+)vector,and the resultant multi-epitope construct was successfully cloned in silico.Results:The fnal construct had a length of 486 bp,an instability index of 23.26,a theoretical pI of 9.34,a molecular weight of 16.5 kDa,and a Z-score of–3.41.Conclusions:The multi-epitope peptide construct could be a conceptual framework for creating a C.sakazakii peptide-based detection kit,which has the potential to provide fast and effcient detection.However,there is a need for additional validation through the in vitro and in vivo techniques.
文摘Atherosclerosis is a severe cardiovascular disease followed by the accumulation of atherosclerotic plaques within the lumen of blood vessels resulting in reduced blood flow thus initiating a series of events.Conventional therapies for atherosclerosis encounter multiple chal-lenges,especially difficulty in precisely concentrating in certain affected regions and the potential for unwanted side effects.Consequently,scientists are focused on developing nanoformulations for atherosclerosis diagnosis and therapy.Peptide-based nanomedi-cines improve conventional therapies by offering improved structural and therapeutic stability and enabling target-specific delivery.Their inherent biocompatibility and biodegradability additionally render them desirable materials intended for in vivo use.This review manu-script aims to provide an in-depth overview of peptide-based nano-medicines for atherosclerosis,focusing on targeted cells like endothelial cells,macrophages,and monocytes and their interaction with different plaque components.Moreover,the manuscript also highlights the latest progress in multimodal techniques and provides a comprehensive overview of limitations associated with their practical implementation.
基金the Canadian Institutes of Health Research(CIHR)Foundation Grant FDN-167274Natural Sciences and Engineering Research Council of Canada(NSERC)Discovery Grant(RGPIN 326982-10)Stem Cell Network Impact Award 920530 and National Institutes of Health Grant 2R01 HL076485.
文摘The substantial economic impact of non-healing wounds,scarring,and burns stemming from skin injuries is evident,resulting in a financial burden on both patients and the healthcare system.This review paper provides an overview of the skin’s vital role in guarding against various environmental challenges as the body’s largest protective organ and associated developments in biomaterials for wound healing.We first introduce the composition of skin tissue and the intricate processes of wound healing,with special attention to the crucial role of immunomodulation in both acute and chronic wounds.This highlights how the imbalance in the immune response,particularly in chronic wounds associated with underlying health conditions such as diabetes and immunosuppression,hinders normal healing stages.Then,this review distinguishes between traditional wound-healing strategies that create an optimal microenvironment and recent peptide-based biomaterials that modulate cellular processes and immune responses to facilitate wound closure.Additionally,we highlight the importance of considering the stages of wounds in the healing process.By integrating advanced materials engineering with an in-depth understanding of wound biology,this approach holds promise for reshaping the field of wound management and ultimately offering improved outcomes for patients with acute and chronic wounds.
