Iridium(Ⅲ)complexes are alternative bioimaging probes due to their tunable photophysical properties,but are limited by poor cell penetrability and high cytotoxicity.Recently,iridium(Ⅲ)-peptide bioconjugates have rec...Iridium(Ⅲ)complexes are alternative bioimaging probes due to their tunable photophysical properties,but are limited by poor cell penetrability and high cytotoxicity.Recently,iridium(Ⅲ)-peptide bioconjugates have received significant attention as bifunctional molecules in bioanalytical and biomedical fields.Conjugation to peptides endows iridium(Ⅲ)complexes with specificity,potentially overcoming the side effects and drug resistance of metallodrugs,whilst enhancing cellular uptake due to the improved cell penetrability,low cytotoxicity and targetability of peptides.In this review,we briefly introduce the interactions between iridium(Ⅲ)complexes and amino acids/peptides,including coordination to amino acids and detection and/or inhibition of peptides.We describe imaging applications of iridium(Ⅲ)-peptide bioconjugates,involving direct coordination of functional peptides or ligand modification,for targeted imaging.Next,we present therapeutic and theranostic applications of iridium(Ⅲ)-peptide bioconjugates through targeting of DNA and proteins.Finally,we outline the challenges and future opportunities in the development of iridium(Ⅲ)-peptide bioconjugates for precision medicine.展开更多
The resulting product of biocoupling is a bioconjugate,typically formed by linking molecules to proteins,oligosaccharides,nucleic acids,or synthetic polymers.By conjugating fluorescent probes with bioactive molecules ...The resulting product of biocoupling is a bioconjugate,typically formed by linking molecules to proteins,oligosaccharides,nucleic acids,or synthetic polymers.By conjugating fluorescent probes with bioactive molecules via click chemistry or bioorthogonal reaction,functional materials with high specificity,sensitivity,and accuracy can be developed.A particularly promising strategy involves the use of aggregation-induced emission(AIE)fluorophores,which exhibit augmented luminescence intensity and excellent photostability when in the aggregated state,making them especially suitable for bioimaging and biosensing applications.The rapid expansion of AIE active bioconjugates now calls for a comprehensive review to summarize and systematize recent advances.In this review,we direct our focus toward the biosensing,bioimaging,and therapeutic applications of AIE active bioconjugates prepared via click chemistry or bioorthogonal reactions.We anticipate that this overview will promote the development of versatile AIE bioconjugates and inspire further innovations in bioorthogonal chemistry for biomedical applications.展开更多
We demonstrate improved peptide linkers which allow both conjugation to biomolecules such as DNA and self-assembly with luminescent semiconductor quantum dots.A hexahistidine peptidyl sequence was generated by standar...We demonstrate improved peptide linkers which allow both conjugation to biomolecules such as DNA and self-assembly with luminescent semiconductor quantum dots.A hexahistidine peptidyl sequence was generated by standard solid phase peptide synthesis and modified with the succinimidyl ester of iodoacetamide to yield a thiol-reactive iodoacetyl polyhistidine linker.The reactive peptide was conjugated to dye-labeled thiolated DNA which was utilized as a model target biomolecule.Agarose gel electrophoresis and fluorescence resonance energy transfer analysis confirmed that the linker allowed the DNA to self-assemble with quantum dots via metal-affinity driven coordination.In contrast to previous peptidyl linkers that were based on disulfide exchange and were thus labile to reduction,the reactive haloacetyl chemistry demonstrated here results in a more stable thioether bond linking the DNA to the peptide which can withstand strongly reducing environments such as the intracellular cytoplasm.As thiol groups occur naturally in proteins,can be engineered into cloned proteins,inserted into nascent peptides or added to DNA during synthesis,the chemistry demonstrated here can provide a simple method for self-assembling a variety of stable quantum dot bioconjugates.展开更多
A facile and efficient strategy has been developed to fabricate a multifunctional,theranostic anticancer drug delivery platform featuring active targeting,controlled drug release and fluorescence imaging for real-time...A facile and efficient strategy has been developed to fabricate a multifunctional,theranostic anticancer drug delivery platform featuring active targeting,controlled drug release and fluorescence imaging for real-time control of delivery.To this end,thermo sensitive poly(N-isopropyl acrylamide)(PNIPAM)nanospheres are decorated with peptide-Au cluster conjugates as a smart nanomedicine platform.A sophisticated trifunctional peptide is designed to release the anticancer drug doxorubicin(DOX),target cells and reduce Au^3+ions to form luminescent Au cluste rs.Importantly,the peptide-Au cluster moieties are attached to the PNIPAM nanospheres via amide bonds rather than noncovalent interactions,significantly improving their stability in biological medium and drug release efficiency.The in vitro experiments showed that DOX was released in an efficient and controlled manner under physiological conditions.展开更多
Objective:This study aimed to describe,optimize and evaluate a method for preparing multivalent conjugate vaccines by simultaneous conjugation of two different bacterial capsular polysaccharides(CPs)with tetanus toxoi...Objective:This study aimed to describe,optimize and evaluate a method for preparing multivalent conjugate vaccines by simultaneous conjugation of two different bacterial capsular polysaccharides(CPs)with tetanus toxoid(TT)as bivalent conjugates.Methods:Different molecular weights(MWs)of polysaccharides,activating agents and capsular polysaccharide/protein(CP/Pro)ratio that may influence conjugation and immunogenicity were investigated and optimized to prepare the bivalent conjugate bulk.Using the described method and optimized parameters,a 20-valent pneumococcal conjugate vaccine and a bivalent meningococcal vaccine were developed and their effectiveness was compared to that of corresponding licensed vaccines in rabbit or mouse models.Results:The immunogenicity test revealed that polysaccharides with lower MWs were better for Pn1-TT-Pn3 and MenA-TT-MenC,while higher MWs were superior for Pn4-TT-Pn14,Pn6A-TT-Pn6B,Pn7F-TT-Pn23F and Pn8-TT-Pn11A.For activating polysaccharides,1-cyano-4-dimethylaminopyridinium tetrafluoroborate(CDAP)was superior to cyanogen bromide(CNBr),but for Pn1,Pn3 and MenC,N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride(EDAC)was the most suitable option.For Pn6A-TT-Pn6B and Pn8-TT-Pn11A,rabbits immunized with bivalent conjugates with lower CP/Pro ratios showed significantly stronger CP-specific antibody responses,while for Pn4-TT-Pn14,higher CP/Pro ratio was better.Instead of interfering with the respective immunological activity,our bivalent conjugates usually induced higher IgG titers than their monovalent counterparts.Conclusion:The result indicated that the described conjugation technique was feasible and efficacious to prepare glycoconjugate vaccines,laying a solid foundation for developing extended-valent multivalent or combined conjugate vaccines without potentially decreased immune function.展开更多
Folate receptor(FR)overexpression occurs in a variety of cancers,including pancreatic cancer.In addition,enhanced macropinocytosis exists in K-Ras mutant pancreatic cancer.Furthermore,the occurrence of intensive desmo...Folate receptor(FR)overexpression occurs in a variety of cancers,including pancreatic cancer.In addition,enhanced macropinocytosis exists in K-Ras mutant pancreatic cancer.Furthermore,the occurrence of intensive desmoplasia causes a hypoxic microenvironment in pancreatic cancer.In this study,a novel FR-directed,macropinocytosis-enhanced,and highly cytotoxic bioconjugate folate(F)-human serum albumin(HSA)-apoprotein of lidamycin(LDP)-active enediyne(AE)derived from lidamycin was designed and prepared.F-HSA-LDP-AE consisted of four moieties:F,HSA,LDP,and AE.F-HSA-LDP presented high binding efficiency with the FR and pancreatic cancer cells.Its uptake in wild-type cells was more extensive than in K-Ras mutant-type cells.By in vivo optical imaging,F-HSA-LDP displayed prominent tumor-specific biodistribution in pancreatic cancer xenograft-bearing mice,showing clear and lasting tumor localization for 360 h.In the MTT assay,F-HSA-LDP-AE demonstrated potent cytotoxicity in three types of pancreatic cancer cell lines.It also induced apoptosis and caused G2/M cell cycle arrest.F-HSALDP-AE markedly suppressed the tumor growth of AsPc-1 pancreatic cancer xenografts in athymic mice.At well-tolerated doses of 0.5 and 1 mg/kg,(i.v.,twice),the inhibition rates were 91.2%and 94.8%,respectively(P<0.01).The results of this study indicate that the F-HSA-LDP multi-functional bioconjugate might be effective for treating K-Ras mutant pancreatic cancer.展开更多
Herein,we report the facile conjugation between proteins and water-soluble [60]fullerene derivatives(DC_(60)) under native conditions using SpyTag as a reactive handle.Water-soluble [60] fullerene derivatives were fir...Herein,we report the facile conjugation between proteins and water-soluble [60]fullerene derivatives(DC_(60)) under native conditions using SpyTag as a reactive handle.Water-soluble [60] fullerene derivatives were first prepared via sequential Bingel-Hirsch reaction and "clicked" with SpyTag to give DC_(60)-SpyTag for native conjugation with proteins by the highly efficient SpyTag-SpyCatcher chemistry.The bioconjugation was confirmed by MALDI-TOF MS spectra and SDS-PAGE analysis.The TEM and UVvis spectroscopic study further revealed that the DC_(60) could alter the optical performance and induce aggregation of the target proteins.It thus provides a general and robust method for modifying proteins with C_(60) derivatives and could potentially be adapted for native conjugation between proteins and other nonbiological motifs as well.展开更多
Nucleases play an important role in molecular biology, for example, in DNA sequencing. Synthetic polyamide conjugates can be considered as a novel tool for the selective inhibition of gene expressions and also as pote...Nucleases play an important role in molecular biology, for example, in DNA sequencing. Synthetic polyamide conjugates can be considered as a novel tool for the selective inhibition of gene expressions and also as potential drugs in anticancer or antiviral chemotherapy. In this article, the synthesis of a novel minor-groove targeting artificial nuclease, an oligopyrrol-containing compound, has been reported. It was found that this novel compound can bind DNA in AT-rich minor groove with high affinity and site specificity. DNA binding behavior was determined by using UV-Vis and CD. It is indicated that compound 6 can enhance the Tm, of DNA from 80.4 ℃ to 84. 4 ℃ and that it possesses a high binding constant value（Kb =3.05 × 10^4 L/mol）.展开更多
A generic method was described to change surface biocompatibihty by introducing reactive functional groups onto surfaces of polymeric substrates and covalently binding them with biomolecules.A block copolymer with pro...A generic method was described to change surface biocompatibihty by introducing reactive functional groups onto surfaces of polymeric substrates and covalently binding them with biomolecules.A block copolymer with protected carboxylic acid functionality,poly（styrene-b-tert-butyl acrylate）（PS-PtBA）,was spin coated from solutions in toluene on a bioinert polystyrene（PS） substrate to form a bilayer structure：a surface layer of the poly（tert-butyl acrylate）（PtBA） blocks that order at the air-polymer interface and a bottom layer of the PS blocks that entangle with the PS substrate.The thickness of the PtBA layer and the area density of tert-butyl ester groups of PtBA increased linearly with the concentration of the spin coating solution until a 2 nm saturated monolayer coverage of PtBA was achieved at the concentration of 0.4%W/W.The protected carboxylic acid groups were generated by exposing the tert-butyl ester groups of PtBA to trifluoroacetic acid （TFA） for bioconjugation with FMRF peptides via amide bonds.The yield of the bioconjugation reaction for the saturated surface was calculated to be 37.1%based on X-ray photoelectron spectroscopy（XPS） measurements.The success of each functionalization step was demonstrated and characterized by XPS and contact angle measurements.This polymer functionalization/modification concept can be virtually applied to any polymeric substrate by choosing appropriate functional block copolymers and biomolecules to attain novel biocompatibility.展开更多
Surface-enhanced Raman scattering(SERS)spectroscopy is presented as a sensitive and spe-cific molecular tool for clinical diagnosis and prognosis monitoring of various diseases including cancer.In order for clinical a...Surface-enhanced Raman scattering(SERS)spectroscopy is presented as a sensitive and spe-cific molecular tool for clinical diagnosis and prognosis monitoring of various diseases including cancer.In order for clinical application of SERS technique,an ideal method of bulk synthesis of SERS nanoparticles is necessary to obtain sensitive,stable and highly reproducible Raman signals.In this contribution,we determined the ideal conditions for bulk synthesis of Raman reporter(Ra)molecules embedded silver-gold core-shell nanoparticles(Au@Ra@AgNPs)using hydroquinone as reducing agent of silver nitrate.By using UV-Vis spectroscopy,Raman spectroscopy and transmission electron microscopy(TEM),we found that a 2∶1 ratio of silver nitrate to hydroquinone is ideal for a uniform silver coating with a strong and stable Raman signal.Through stability testing of the optimized Au@Ra@AgNPs over a two-week period,these SERS nanotags were found to be stable with minimal signal change occurred.The sta-bility of antibody linked SERS nanotags is also crucial for cancer and disease diagnosis,thus,we further conjugated the as-prepared SERS nanotags with anti-EpCAM antibody,in which the stability of bioconjugated SERS nanotags was tested over eight days.Both UV-Vis and SERS spectroscopy showed stable absorption and Raman signals on the anti-EpCAM conju-gated SERS nanotags,indicating the great potential of the synthesized SERS nanotags for future applications which require large,reproducible and uniform quantities in order for cancer biomarker diagnosis and monitoring.展开更多
Monodispersed microspheres with polystyrene as the core and poly（acrylamide-co-N-acryloxysuccinirnide） as the shell were synthesized by a two-step surfactant-free emulsion copolymerization.The core-shell morphology ...Monodispersed microspheres with polystyrene as the core and poly（acrylamide-co-N-acryloxysuccinirnide） as the shell were synthesized by a two-step surfactant-free emulsion copolymerization.The core-shell morphology of the microspheres was shown by scanning electron microscopy and transmission electron microscopy.Rabbit immunoglobulin G （as antigen） was covalently coupled onto the microspheres by the reaction between succinimide-activated ester groups on the shell of the microspheres and amino groups of the antigen molecules.The size of particles was characterized by dynamic light scattering technique and was found to vary upon bioconjugation and interaction with proteins.The binding process was shown to be specific to goat anti-rabbit immunoglobulin G（as antibody） and reversible upon the addition of free antigen into the system.展开更多
For a significant duration,enhancing the efficacy of cancer therapy has remained a critical concern.Magnetotactic bacteria(MTB),often likened to micro-robots,hold substantial promise as a drug delivery system.MTB,clas...For a significant duration,enhancing the efficacy of cancer therapy has remained a critical concern.Magnetotactic bacteria(MTB),often likened to micro-robots,hold substantial promise as a drug delivery system.MTB,classified as anaerobic,aquatic,and gram-negative microorganisms,exhibit remarkable motility and precise control over their internal biomineralization processes.This unique ability results in the formation of magnetic nanoparticles arranged along filamentous structures in a catenary fashion,enclosed within a membrane.These bacteria possess distinctive biochemical properties that facilitate their precise positioning within complex environments.By harnessing these biochemical attributes,MTB could potentially offer substantial advantages in the realm of cancer therapy.This article reviews the drug delivery capabilities of MTB in tumor treatment and explores various applications based on their inherent properties.The objective is to provide a comprehensive understanding of MTB-driven drug delivery and stimulate innovative insights in this field.展开更多
Chemoselective amine bioco njugation has long been a challenge for native protein modification.Inspired by Thiele’s seminal discovery,Li and co-workers recently developed an orto-phthalaldehyde(OPA)based reagent for ...Chemoselective amine bioco njugation has long been a challenge for native protein modification.Inspired by Thiele’s seminal discovery,Li and co-workers recently developed an orto-phthalaldehyde(OPA)based reagent for labeling the amino group of a protein.Here we report an expeditious and scalable synthesis of a Li-Thiele reagent featuring an arene construction strategy.The reagent contains an alkyne side chain as a handle for secondary modification.展开更多
Amino acid bioconjugation technology has emerged as a pivotal tool for linking small-molecule fragments with proteins,antibodies,and even cells.The study in Nature by Chang and Toste introduces a redox-based strategy ...Amino acid bioconjugation technology has emerged as a pivotal tool for linking small-molecule fragments with proteins,antibodies,and even cells.The study in Nature by Chang and Toste introduces a redox-based strategy for tryptophan bioconjugation,employing N-sulfonyloxaziridines as oxidative cyclization reagents,demonstrating high efficiency comparable to traditional click reactions.Meanwhile,this tool provides feasible methods for investigating the mechanisms underlying functional tryptophan-related biochemical processes,paving the way for protein function exploration,activity-based proteomics for functional amino acid identification and characterization,and even the design of covalent inhibitors.展开更多
Polyethylene glycol(PEG)is a polymer with different molecular weights formed by the polymerization of ethylene oxide monomers.Due to its ability to significantly reduce the immunogenicity of protein drugs and extend t...Polyethylene glycol(PEG)is a polymer with different molecular weights formed by the polymerization of ethylene oxide monomers.Due to its ability to significantly reduce the immunogenicity of protein drugs and extend their half-life,as well as its high safety profile,it has been approved by the U.S.Food and Drug Administration(FDA)as the gold standard for delivering protein drugs.Although numerous PEGylated protein drugs have been marketed,the focus of research on PEGylated protein drugs has primarily been on reducing immunogenicity and extending in vivo circulation half-life.However,the understanding of how PEG modification affects the structure and function of proteins is still limited,with“activity”often being the sole criterion for evaluating changes in protein structure and function.A deeper exploration of the existence and interaction between PEG chains and proteins is of great significance for understanding the properties exhibited by PEGylated proteins.This review summarizes strategies for PEG site-specific modification of proteins,the interaction states between PEG and proteins,and the effects of PEG chains on protein spatial structure,solubility,activity,and thermal stability.It also summarizes the characterization techniques for PEG-protein interactions,aiming to predict or explain the functions of PEGylated protein drugs through the analysis of PEG-protein interactions.展开更多
Since the emergence of cancer nanomedicine, researchers have had intense interest in developing nanoparticles （NPs） that can specifically target diseased sites while avoiding healthy tissue to mitigate the off-targe...Since the emergence of cancer nanomedicine, researchers have had intense interest in developing nanoparticles （NPs） that can specifically target diseased sites while avoiding healthy tissue to mitigate the off-target effects seen with conventional treatments like chemotherapy. Initial endeavors focused on the bioconjugation of targeting agents to NPs, and more recently, researchers have begun to develop biomimetic NP platforms that can avoid immune recognition to maximally accumulate in tumors. In this review, we describe the advantages and limitations of each of these targeting strategies. First, we review developments in bioconjugation strategies, where NPs are coated with biomolecules such as antibodies, aptamers, peptides, and small molecules to enable cell-specific binding. While bioconjugated NPs offer many exciting features and have improved pharmacokinetics and biodistribution relative to unmodified NPs, they are still recognized by the body as ＂foreign＂, resulting in their clearance by the mononuclear phagocytic system （MPS）. To overcome this limitation, researchers have recently begun to investigate biomimetic approaches that can hide NPs from immune recognition and reduce clearance by the MPS. These biomimetic NPs fall into two distinct categories： synthetic NPs that present naturally occurring structures, and NPs that are completely disguised by natural structures. Overall bioconjugated and biomimetic NPs have substantial potential to improve upon conventional treatments by reducing off-target effects through site-specific delivery. and they show great promise for future standards of care. Here, we provide a summary of each strategy, discuss considerations for their design moving forward, and highlight their potential clinical impact on cancer therapy.展开更多
Supramolecular proteins are generated using a limited set of twenty amino acids,but have distinctive functionalities which arise from the sequential arrangement of amino acids configured to exquisite three-dimensional...Supramolecular proteins are generated using a limited set of twenty amino acids,but have distinctive functionalities which arise from the sequential arrangement of amino acids configured to exquisite three-dimensional structures.Viruses,virus-like particles,ferritins,enzyme complexes,cellular micro-compartments,and other supramolecular protein assemblies exemplify these systems,with their precise arrangements of tens to hundreds of molecules into highly organized scaffolds for nucleic acid packaging,metal storage,catalysis or sequestering reactions at the nanometer scale.These versatile protein systems,dubbed as bionanoparticles(BNPs),have attracted materials scientists to seek new opportunities with these pre-fabricated templates in a wide range of nanotechnology-related applications.Here,we focus on some of the key modification strategies that have been utilized,ranging from basic protein conjugation techniques to more novel strategies,to expand the functionalities of these multimeric protein assemblies.Ultimately,in combination with molecular cloning and sophisticated chemistries,these BNPs are being incorporated into many applications ranging from functional materials to novel biomedical drug designs.展开更多
Using biological templates to build one-dimensional functional materials holds great promise in developing nanosized electrical devices,sensors,catalysts,and energy storage units.In this communication,we report a vers...Using biological templates to build one-dimensional functional materials holds great promise in developing nanosized electrical devices,sensors,catalysts,and energy storage units.In this communication,we report a versatile assembly process for the preparation of water-soluble conductive polyaniline(PANi)/M13 composite nanowires by employing the bacteriophage M13 as a template.The surface lysine residues of M13 can be derivatized with carboxylic groups to improve its binding ability to the aniline;the resulting modifi ed M13 is denoted as m-M13.Highly negatively-charged poly(sulfonated styrene)was used both as a dopant acid and a stabilizing agent to enhance the stability of the composite fi bers in aqueous solution.A transparent solution of the conductive PANi/m-M13 composite fi bers can be readily obtained without any further purifi cation step.The fi bers can be easily fabricated into thin conductive fi lms due to their high aspect ratio and good solubility in aqueous solution.This synthesis discloses a unique and versatile way of using bionanorods to produce composite fi brillar materials with narrow dispersity,high aspect ratio,and high processibility,which may have many potential applications in electronics,optics,sensing,and biomedical engineering.展开更多
The synthesis of norvancomycin (NVan)-capped silver nanoparticles (Ag@NVan) and their notable in vitro antibacterial activities against E. coli, a Gram-negative bacterial strain (GNB), are reported here. Mercaptoaceti...The synthesis of norvancomycin (NVan)-capped silver nanoparticles (Ag@NVan) and their notable in vitro antibacterial activities against E. coli, a Gram-negative bacterial strain (GNB), are reported here. Mercaptoacetic acid-stabilized spherical silver nanoparticles with a diameter of 16±4 nm are prepared by a simple chemical reaction. The formation process of the silver nanoparticles is investigated by UV-visible (UV-vis) spectroscopy and transmission electron microscopy (TEM). NVan is then grafted to the terminal carboxyl of the mercaptoacetic acid in the presence of N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDAC). The TEM images of single bacteria treated with Ag@NVan show that plenty of Ag@NVan aggregate in the cell wall of E. coli. A possible antibacterial mechanism is proposed that silver nanoparticles may help destroy the stability of the outer membrane of E. coli, which makes NVan easier to bind to the nether part of the peptidoglycan structure. The antibacterial activities of silver nanoparticles on their own, together with the rigid polyvalent interaction between Ag@NVan and cell wall, enables Ag@NVan to be an effective inhibitor of GNB. This kind of bionanocomposites might be used as novel bactericidal materials and we also provide an effective synthesis method for preparing functional bioconjugated nanoparticles here.展开更多
The ACE inhibitory peptides have been characterized from the enzymatic digestion product of bighead carp protein and bioconjugated with graphene oxide(GO)to enhance its activity.The results showed that aspartic acid a...The ACE inhibitory peptides have been characterized from the enzymatic digestion product of bighead carp protein and bioconjugated with graphene oxide(GO)to enhance its activity.The results showed that aspartic acid and glutamic acid had the highest levels in ultrafiltration fractions(<5 kDa),where eight potential ACE inhibitory peptides were also identified(ADSNHKAF,KLWHHTF,LLRLHF,PPSEPTKL,VEKFPLF,YLRLHF,YYKLKPLL,YYKLKPML).Among the eight peptides,YLRLHF showed the best ACE inhibitory activity(IC50=121.90μM)and was a competitive inhibitor.Molecular docking experiments showed that YLRLHF formed four hydrogen bond interactions in the ACE protein pocket,coordination bonding with Zn^(2+),and π-πconjugation interactions to His421.GO elevated the ACE inhibitory activity of YLRLHF(at 0.1 mg/mL)from 43.36%to 51.72%.The structural characterization results obtained from FI-IR,XPS,SEM,and TEM demonstrated the successful combination of GO and YLRLHF.Additionally,biocouples of ACE inhibitory peptides from bighead carp proteins with GO might be potential candidates for future functional foods and antihypertensive drugs.展开更多
基金supported by the National Natural Science Foundation of China(22101230)the Fundamental Research Funds for the Central Universities(D5000230060)+7 种基金the Key Research and Development Program of Shaanxi(2024SF-YBXM-181,2024SF-YBXM-418)Shanghai Sailing Program(21YF1451200)the Natural Science Foundation of Chongqing,China(cstc2021jcyj-msxm2073)the Shaanxi Fundamental Science Research Project for Chemistry&Biology(22JHQ082)the Guangdong Basic and Applied Basic Research Foundation(2021A1515110840,2023A1515011871)the Science and Technology Development Fund,Macao SAR,China(File no.005/2023/SKL,0020/2022/A1,0045/2023/AMJ,0032/2023/RIB2)the University of Macao,Macao SAR,China(File no.MYRG2020-00017-ICMS,MYRG2022-00137-ICMS,MYRG-GRG2023-00194-ICMS-UMDF)the State Key Laboratory of Quality Research in Chinese Medicine,the University of Macao,Macao SAR,China(File no.SKL-QRCM-IRG2023-025).
文摘Iridium(Ⅲ)complexes are alternative bioimaging probes due to their tunable photophysical properties,but are limited by poor cell penetrability and high cytotoxicity.Recently,iridium(Ⅲ)-peptide bioconjugates have received significant attention as bifunctional molecules in bioanalytical and biomedical fields.Conjugation to peptides endows iridium(Ⅲ)complexes with specificity,potentially overcoming the side effects and drug resistance of metallodrugs,whilst enhancing cellular uptake due to the improved cell penetrability,low cytotoxicity and targetability of peptides.In this review,we briefly introduce the interactions between iridium(Ⅲ)complexes and amino acids/peptides,including coordination to amino acids and detection and/or inhibition of peptides.We describe imaging applications of iridium(Ⅲ)-peptide bioconjugates,involving direct coordination of functional peptides or ligand modification,for targeted imaging.Next,we present therapeutic and theranostic applications of iridium(Ⅲ)-peptide bioconjugates through targeting of DNA and proteins.Finally,we outline the challenges and future opportunities in the development of iridium(Ⅲ)-peptide bioconjugates for precision medicine.
基金supported by the National Key Research and Development Program of China(2024YFA1212100)National Natural Science Foundation of China(52573204,22475134)+2 种基金the Guangdong Basic and Applied Basic Research Foundation(2025A1515010662)the Shenzhen Medical Academy of Research and Translation(B2502003)the Science and Technology Foundation of Shenzhen City(JCYJ20241202124423032,20220809130438001).
文摘The resulting product of biocoupling is a bioconjugate,typically formed by linking molecules to proteins,oligosaccharides,nucleic acids,or synthetic polymers.By conjugating fluorescent probes with bioactive molecules via click chemistry or bioorthogonal reaction,functional materials with high specificity,sensitivity,and accuracy can be developed.A particularly promising strategy involves the use of aggregation-induced emission(AIE)fluorophores,which exhibit augmented luminescence intensity and excellent photostability when in the aggregated state,making them especially suitable for bioimaging and biosensing applications.The rapid expansion of AIE active bioconjugates now calls for a comprehensive review to summarize and systematize recent advances.In this review,we direct our focus toward the biosensing,bioimaging,and therapeutic applications of AIE active bioconjugates prepared via click chemistry or bioorthogonal reactions.We anticipate that this overview will promote the development of versatile AIE bioconjugates and inspire further innovations in bioorthogonal chemistry for biomedical applications.
基金The authors acknowledge Stephen Lee and Ilya Elashvilli of the CB Directorate/Physical S&T Division(DTRA),ONR,NRL,and the NRLNSI for financial support.
文摘We demonstrate improved peptide linkers which allow both conjugation to biomolecules such as DNA and self-assembly with luminescent semiconductor quantum dots.A hexahistidine peptidyl sequence was generated by standard solid phase peptide synthesis and modified with the succinimidyl ester of iodoacetamide to yield a thiol-reactive iodoacetyl polyhistidine linker.The reactive peptide was conjugated to dye-labeled thiolated DNA which was utilized as a model target biomolecule.Agarose gel electrophoresis and fluorescence resonance energy transfer analysis confirmed that the linker allowed the DNA to self-assemble with quantum dots via metal-affinity driven coordination.In contrast to previous peptidyl linkers that were based on disulfide exchange and were thus labile to reduction,the reactive haloacetyl chemistry demonstrated here results in a more stable thioether bond linking the DNA to the peptide which can withstand strongly reducing environments such as the intracellular cytoplasm.As thiol groups occur naturally in proteins,can be engineered into cloned proteins,inserted into nascent peptides or added to DNA during synthesis,the chemistry demonstrated here can provide a simple method for self-assembling a variety of stable quantum dot bioconjugates.
基金financial support from the National Natural Science Foundation of China(NSFC,Nos.51573013,51873016)support from the Shaanxi Natural Science Foundation(No.2018JM2004)+1 种基金NSFC(No.21705129)funded by the Helmholtz association,program Science and Technology of Nanosystems(STN)。
文摘A facile and efficient strategy has been developed to fabricate a multifunctional,theranostic anticancer drug delivery platform featuring active targeting,controlled drug release and fluorescence imaging for real-time control of delivery.To this end,thermo sensitive poly(N-isopropyl acrylamide)(PNIPAM)nanospheres are decorated with peptide-Au cluster conjugates as a smart nanomedicine platform.A sophisticated trifunctional peptide is designed to release the anticancer drug doxorubicin(DOX),target cells and reduce Au^3+ions to form luminescent Au cluste rs.Importantly,the peptide-Au cluster moieties are attached to the PNIPAM nanospheres via amide bonds rather than noncovalent interactions,significantly improving their stability in biological medium and drug release efficiency.The in vitro experiments showed that DOX was released in an efficient and controlled manner under physiological conditions.
文摘Objective:This study aimed to describe,optimize and evaluate a method for preparing multivalent conjugate vaccines by simultaneous conjugation of two different bacterial capsular polysaccharides(CPs)with tetanus toxoid(TT)as bivalent conjugates.Methods:Different molecular weights(MWs)of polysaccharides,activating agents and capsular polysaccharide/protein(CP/Pro)ratio that may influence conjugation and immunogenicity were investigated and optimized to prepare the bivalent conjugate bulk.Using the described method and optimized parameters,a 20-valent pneumococcal conjugate vaccine and a bivalent meningococcal vaccine were developed and their effectiveness was compared to that of corresponding licensed vaccines in rabbit or mouse models.Results:The immunogenicity test revealed that polysaccharides with lower MWs were better for Pn1-TT-Pn3 and MenA-TT-MenC,while higher MWs were superior for Pn4-TT-Pn14,Pn6A-TT-Pn6B,Pn7F-TT-Pn23F and Pn8-TT-Pn11A.For activating polysaccharides,1-cyano-4-dimethylaminopyridinium tetrafluoroborate(CDAP)was superior to cyanogen bromide(CNBr),but for Pn1,Pn3 and MenC,N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride(EDAC)was the most suitable option.For Pn6A-TT-Pn6B and Pn8-TT-Pn11A,rabbits immunized with bivalent conjugates with lower CP/Pro ratios showed significantly stronger CP-specific antibody responses,while for Pn4-TT-Pn14,higher CP/Pro ratio was better.Instead of interfering with the respective immunological activity,our bivalent conjugates usually induced higher IgG titers than their monovalent counterparts.Conclusion:The result indicated that the described conjugation technique was feasible and efficacious to prepare glycoconjugate vaccines,laying a solid foundation for developing extended-valent multivalent or combined conjugate vaccines without potentially decreased immune function.
基金supported by grants from CAMS Innovation Fund for Medical Sciences(Grant No.:2021-I2M-1-026)Scientific Research Project of Tianjin Education Commission(Grant No.:2020KJ140)Tianjin Health Research Project(Grant No.:KJ20017)。
文摘Folate receptor(FR)overexpression occurs in a variety of cancers,including pancreatic cancer.In addition,enhanced macropinocytosis exists in K-Ras mutant pancreatic cancer.Furthermore,the occurrence of intensive desmoplasia causes a hypoxic microenvironment in pancreatic cancer.In this study,a novel FR-directed,macropinocytosis-enhanced,and highly cytotoxic bioconjugate folate(F)-human serum albumin(HSA)-apoprotein of lidamycin(LDP)-active enediyne(AE)derived from lidamycin was designed and prepared.F-HSA-LDP-AE consisted of four moieties:F,HSA,LDP,and AE.F-HSA-LDP presented high binding efficiency with the FR and pancreatic cancer cells.Its uptake in wild-type cells was more extensive than in K-Ras mutant-type cells.By in vivo optical imaging,F-HSA-LDP displayed prominent tumor-specific biodistribution in pancreatic cancer xenograft-bearing mice,showing clear and lasting tumor localization for 360 h.In the MTT assay,F-HSA-LDP-AE demonstrated potent cytotoxicity in three types of pancreatic cancer cell lines.It also induced apoptosis and caused G2/M cell cycle arrest.F-HSALDP-AE markedly suppressed the tumor growth of AsPc-1 pancreatic cancer xenografts in athymic mice.At well-tolerated doses of 0.5 and 1 mg/kg,(i.v.,twice),the inhibition rates were 91.2%and 94.8%,respectively(P<0.01).The results of this study indicate that the F-HSA-LDP multi-functional bioconjugate might be effective for treating K-Ras mutant pancreatic cancer.
基金the financial support from the National Natural Science Foundation of China(Nos.21925102,21991132 and 21674003)supported by Beijing National Laboratory for Molecular Sciences(No.BNLMS-CXXM-202006)Clinical Medicine Plus X Project of Peking University,Fundamental Research Funds for the Central Universities。
文摘Herein,we report the facile conjugation between proteins and water-soluble [60]fullerene derivatives(DC_(60)) under native conditions using SpyTag as a reactive handle.Water-soluble [60] fullerene derivatives were first prepared via sequential Bingel-Hirsch reaction and "clicked" with SpyTag to give DC_(60)-SpyTag for native conjugation with proteins by the highly efficient SpyTag-SpyCatcher chemistry.The bioconjugation was confirmed by MALDI-TOF MS spectra and SDS-PAGE analysis.The TEM and UVvis spectroscopic study further revealed that the DC_(60) could alter the optical performance and induce aggregation of the target proteins.It thus provides a general and robust method for modifying proteins with C_(60) derivatives and could potentially be adapted for native conjugation between proteins and other nonbiological motifs as well.
基金Supported by the National Natural Science Foundation of China(Nos 20132020 and 20572061), the National Science andTechnology Committee of China, the National Ministry of Education of China, and Tsinghua University
文摘Nucleases play an important role in molecular biology, for example, in DNA sequencing. Synthetic polyamide conjugates can be considered as a novel tool for the selective inhibition of gene expressions and also as potential drugs in anticancer or antiviral chemotherapy. In this article, the synthesis of a novel minor-groove targeting artificial nuclease, an oligopyrrol-containing compound, has been reported. It was found that this novel compound can bind DNA in AT-rich minor groove with high affinity and site specificity. DNA binding behavior was determined by using UV-Vis and CD. It is indicated that compound 6 can enhance the Tm, of DNA from 80.4 ℃ to 84. 4 ℃ and that it possesses a high binding constant value（Kb =3.05 × 10^4 L/mol）.
文摘A generic method was described to change surface biocompatibihty by introducing reactive functional groups onto surfaces of polymeric substrates and covalently binding them with biomolecules.A block copolymer with protected carboxylic acid functionality,poly（styrene-b-tert-butyl acrylate）（PS-PtBA）,was spin coated from solutions in toluene on a bioinert polystyrene（PS） substrate to form a bilayer structure：a surface layer of the poly（tert-butyl acrylate）（PtBA） blocks that order at the air-polymer interface and a bottom layer of the PS blocks that entangle with the PS substrate.The thickness of the PtBA layer and the area density of tert-butyl ester groups of PtBA increased linearly with the concentration of the spin coating solution until a 2 nm saturated monolayer coverage of PtBA was achieved at the concentration of 0.4%W/W.The protected carboxylic acid groups were generated by exposing the tert-butyl ester groups of PtBA to trifluoroacetic acid （TFA） for bioconjugation with FMRF peptides via amide bonds.The yield of the bioconjugation reaction for the saturated surface was calculated to be 37.1%based on X-ray photoelectron spectroscopy（XPS） measurements.The success of each functionalization step was demonstrated and characterized by XPS and contact angle measurements.This polymer functionalization/modification concept can be virtually applied to any polymeric substrate by choosing appropriate functional block copolymers and biomolecules to attain novel biocompatibility.
基金This work was supported by the Australian Research Council(ARC)through its Centre of Excellence for Nanoscale BioPhotonics(CE140100003)ARC Discovery Projects(DP200102004).
文摘Surface-enhanced Raman scattering(SERS)spectroscopy is presented as a sensitive and spe-cific molecular tool for clinical diagnosis and prognosis monitoring of various diseases including cancer.In order for clinical application of SERS technique,an ideal method of bulk synthesis of SERS nanoparticles is necessary to obtain sensitive,stable and highly reproducible Raman signals.In this contribution,we determined the ideal conditions for bulk synthesis of Raman reporter(Ra)molecules embedded silver-gold core-shell nanoparticles(Au@Ra@AgNPs)using hydroquinone as reducing agent of silver nitrate.By using UV-Vis spectroscopy,Raman spectroscopy and transmission electron microscopy(TEM),we found that a 2∶1 ratio of silver nitrate to hydroquinone is ideal for a uniform silver coating with a strong and stable Raman signal.Through stability testing of the optimized Au@Ra@AgNPs over a two-week period,these SERS nanotags were found to be stable with minimal signal change occurred.The sta-bility of antibody linked SERS nanotags is also crucial for cancer and disease diagnosis,thus,we further conjugated the as-prepared SERS nanotags with anti-EpCAM antibody,in which the stability of bioconjugated SERS nanotags was tested over eight days.Both UV-Vis and SERS spectroscopy showed stable absorption and Raman signals on the anti-EpCAM conju-gated SERS nanotags,indicating the great potential of the synthesized SERS nanotags for future applications which require large,reproducible and uniform quantities in order for cancer biomarker diagnosis and monitoring.
基金supported by the National Natural Science Foundation of China(Nos.20328407,50673045) and the Canada Research Chair program
文摘Monodispersed microspheres with polystyrene as the core and poly（acrylamide-co-N-acryloxysuccinirnide） as the shell were synthesized by a two-step surfactant-free emulsion copolymerization.The core-shell morphology of the microspheres was shown by scanning electron microscopy and transmission electron microscopy.Rabbit immunoglobulin G （as antigen） was covalently coupled onto the microspheres by the reaction between succinimide-activated ester groups on the shell of the microspheres and amino groups of the antigen molecules.The size of particles was characterized by dynamic light scattering technique and was found to vary upon bioconjugation and interaction with proteins.The binding process was shown to be specific to goat anti-rabbit immunoglobulin G（as antibody） and reversible upon the addition of free antigen into the system.
基金supported by the National Natural Science Foundation of China(No.3190110313 to K.Ma)Special Foundation of President of the Chinese Academy of Sciences(No.YZJJ2022QN_(4)4)+2 种基金HFIPS Director’s Fund(Nos.E16CWK123X1YZJJQY202201)the Heye Health Technology Chong Ming Project(No.HYCMP-2022012 to Y.Wang)。
文摘For a significant duration,enhancing the efficacy of cancer therapy has remained a critical concern.Magnetotactic bacteria(MTB),often likened to micro-robots,hold substantial promise as a drug delivery system.MTB,classified as anaerobic,aquatic,and gram-negative microorganisms,exhibit remarkable motility and precise control over their internal biomineralization processes.This unique ability results in the formation of magnetic nanoparticles arranged along filamentous structures in a catenary fashion,enclosed within a membrane.These bacteria possess distinctive biochemical properties that facilitate their precise positioning within complex environments.By harnessing these biochemical attributes,MTB could potentially offer substantial advantages in the realm of cancer therapy.This article reviews the drug delivery capabilities of MTB in tumor treatment and explores various applications based on their inherent properties.The objective is to provide a comprehensive understanding of MTB-driven drug delivery and stimulate innovative insights in this field.
基金supported by Ministry of Science and Technology (National Key Research and Development Program of China,No.2018YFA0901900)the National Natural Science Foundation of China (Nos.21931014,21525209, 21621002,21772225,and 21761142003)+4 种基金Chinese Academy of Sciences (Strategic Priority Research Program,No.XDB20000000International Partner Program,No.121731KYSB20190039Key Research Program of Frontier Sciences,No.QYZDB-SSW-SLH040)Science and Technology Commission of Shanghai Municipality (No.17XD1404600)K.C.Wong Education Foundation。
文摘Chemoselective amine bioco njugation has long been a challenge for native protein modification.Inspired by Thiele’s seminal discovery,Li and co-workers recently developed an orto-phthalaldehyde(OPA)based reagent for labeling the amino group of a protein.Here we report an expeditious and scalable synthesis of a Li-Thiele reagent featuring an arene construction strategy.The reagent contains an alkyne side chain as a handle for secondary modification.
基金financial support from the National Natural Science Foundation of China(82374020 and 82374155)Science and Technology Department of Sichuan Province(2023ZYD0054 and 2024NSFTD0023)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202209).
文摘Amino acid bioconjugation technology has emerged as a pivotal tool for linking small-molecule fragments with proteins,antibodies,and even cells.The study in Nature by Chang and Toste introduces a redox-based strategy for tryptophan bioconjugation,employing N-sulfonyloxaziridines as oxidative cyclization reagents,demonstrating high efficiency comparable to traditional click reactions.Meanwhile,this tool provides feasible methods for investigating the mechanisms underlying functional tryptophan-related biochemical processes,paving the way for protein function exploration,activity-based proteomics for functional amino acid identification and characterization,and even the design of covalent inhibitors.
基金supported by National Natural Science Foundation of China(No.82173788).
文摘Polyethylene glycol(PEG)is a polymer with different molecular weights formed by the polymerization of ethylene oxide monomers.Due to its ability to significantly reduce the immunogenicity of protein drugs and extend their half-life,as well as its high safety profile,it has been approved by the U.S.Food and Drug Administration(FDA)as the gold standard for delivering protein drugs.Although numerous PEGylated protein drugs have been marketed,the focus of research on PEGylated protein drugs has primarily been on reducing immunogenicity and extending in vivo circulation half-life.However,the understanding of how PEG modification affects the structure and function of proteins is still limited,with“activity”often being the sole criterion for evaluating changes in protein structure and function.A deeper exploration of the existence and interaction between PEG chains and proteins is of great significance for understanding the properties exhibited by PEGylated proteins.This review summarizes strategies for PEG site-specific modification of proteins,the interaction states between PEG and proteins,and the effects of PEG chains on protein spatial structure,solubility,activity,and thermal stability.It also summarizes the characterization techniques for PEG-protein interactions,aiming to predict or explain the functions of PEGylated protein drugs through the analysis of PEG-protein interactions.
文摘Since the emergence of cancer nanomedicine, researchers have had intense interest in developing nanoparticles （NPs） that can specifically target diseased sites while avoiding healthy tissue to mitigate the off-target effects seen with conventional treatments like chemotherapy. Initial endeavors focused on the bioconjugation of targeting agents to NPs, and more recently, researchers have begun to develop biomimetic NP platforms that can avoid immune recognition to maximally accumulate in tumors. In this review, we describe the advantages and limitations of each of these targeting strategies. First, we review developments in bioconjugation strategies, where NPs are coated with biomolecules such as antibodies, aptamers, peptides, and small molecules to enable cell-specific binding. While bioconjugated NPs offer many exciting features and have improved pharmacokinetics and biodistribution relative to unmodified NPs, they are still recognized by the body as ＂foreign＂, resulting in their clearance by the mononuclear phagocytic system （MPS）. To overcome this limitation, researchers have recently begun to investigate biomimetic approaches that can hide NPs from immune recognition and reduce clearance by the MPS. These biomimetic NPs fall into two distinct categories： synthetic NPs that present naturally occurring structures, and NPs that are completely disguised by natural structures. Overall bioconjugated and biomimetic NPs have substantial potential to improve upon conventional treatments by reducing off-target effects through site-specific delivery. and they show great promise for future standards of care. Here, we provide a summary of each strategy, discuss considerations for their design moving forward, and highlight their potential clinical impact on cancer therapy.
文摘Supramolecular proteins are generated using a limited set of twenty amino acids,but have distinctive functionalities which arise from the sequential arrangement of amino acids configured to exquisite three-dimensional structures.Viruses,virus-like particles,ferritins,enzyme complexes,cellular micro-compartments,and other supramolecular protein assemblies exemplify these systems,with their precise arrangements of tens to hundreds of molecules into highly organized scaffolds for nucleic acid packaging,metal storage,catalysis or sequestering reactions at the nanometer scale.These versatile protein systems,dubbed as bionanoparticles(BNPs),have attracted materials scientists to seek new opportunities with these pre-fabricated templates in a wide range of nanotechnology-related applications.Here,we focus on some of the key modification strategies that have been utilized,ranging from basic protein conjugation techniques to more novel strategies,to expand the functionalities of these multimeric protein assemblies.Ultimately,in combination with molecular cloning and sophisticated chemistries,these BNPs are being incorporated into many applications ranging from functional materials to novel biomedical drug designs.
基金We are grateful for financial support from NSF-DMR-0706431,NSF career award,US DoD,and the W.M.Keck Foundation.This manuscript has been approved by the U.S.Army Natick Soldier Research,Development and Engineering Center for unlimited distribution(PAO#08-107).
文摘Using biological templates to build one-dimensional functional materials holds great promise in developing nanosized electrical devices,sensors,catalysts,and energy storage units.In this communication,we report a versatile assembly process for the preparation of water-soluble conductive polyaniline(PANi)/M13 composite nanowires by employing the bacteriophage M13 as a template.The surface lysine residues of M13 can be derivatized with carboxylic groups to improve its binding ability to the aniline;the resulting modifi ed M13 is denoted as m-M13.Highly negatively-charged poly(sulfonated styrene)was used both as a dopant acid and a stabilizing agent to enhance the stability of the composite fi bers in aqueous solution.A transparent solution of the conductive PANi/m-M13 composite fi bers can be readily obtained without any further purifi cation step.The fi bers can be easily fabricated into thin conductive fi lms due to their high aspect ratio and good solubility in aqueous solution.This synthesis discloses a unique and versatile way of using bionanorods to produce composite fi brillar materials with narrow dispersity,high aspect ratio,and high processibility,which may have many potential applications in electronics,optics,sensing,and biomedical engineering.
基金Supported by the National Natural Science Foundation of China (Grant No. 50373036)Fok Ying Tung Education Foundation (Grant No. J20040212)
文摘The synthesis of norvancomycin (NVan)-capped silver nanoparticles (Ag@NVan) and their notable in vitro antibacterial activities against E. coli, a Gram-negative bacterial strain (GNB), are reported here. Mercaptoacetic acid-stabilized spherical silver nanoparticles with a diameter of 16±4 nm are prepared by a simple chemical reaction. The formation process of the silver nanoparticles is investigated by UV-visible (UV-vis) spectroscopy and transmission electron microscopy (TEM). NVan is then grafted to the terminal carboxyl of the mercaptoacetic acid in the presence of N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDAC). The TEM images of single bacteria treated with Ag@NVan show that plenty of Ag@NVan aggregate in the cell wall of E. coli. A possible antibacterial mechanism is proposed that silver nanoparticles may help destroy the stability of the outer membrane of E. coli, which makes NVan easier to bind to the nether part of the peptidoglycan structure. The antibacterial activities of silver nanoparticles on their own, together with the rigid polyvalent interaction between Ag@NVan and cell wall, enables Ag@NVan to be an effective inhibitor of GNB. This kind of bionanocomposites might be used as novel bactericidal materials and we also provide an effective synthesis method for preparing functional bioconjugated nanoparticles here.
基金The research was funded by the National Key R&D Program of China(2019YFD0901805).
文摘The ACE inhibitory peptides have been characterized from the enzymatic digestion product of bighead carp protein and bioconjugated with graphene oxide(GO)to enhance its activity.The results showed that aspartic acid and glutamic acid had the highest levels in ultrafiltration fractions(<5 kDa),where eight potential ACE inhibitory peptides were also identified(ADSNHKAF,KLWHHTF,LLRLHF,PPSEPTKL,VEKFPLF,YLRLHF,YYKLKPLL,YYKLKPML).Among the eight peptides,YLRLHF showed the best ACE inhibitory activity(IC50=121.90μM)and was a competitive inhibitor.Molecular docking experiments showed that YLRLHF formed four hydrogen bond interactions in the ACE protein pocket,coordination bonding with Zn^(2+),and π-πconjugation interactions to His421.GO elevated the ACE inhibitory activity of YLRLHF(at 0.1 mg/mL)from 43.36%to 51.72%.The structural characterization results obtained from FI-IR,XPS,SEM,and TEM demonstrated the successful combination of GO and YLRLHF.Additionally,biocouples of ACE inhibitory peptides from bighead carp proteins with GO might be potential candidates for future functional foods and antihypertensive drugs.
