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Visible light cross-linking and bioactive peptides loaded integrated hydrogel with sequential release to accelerate wound healing complicated by bacterial infection

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Nano Research 2024年第3期17卷 1737-1747页

作者： Guiyan Wang Ning Yuan Jun Zhang Man Qin suwei dong Yuguang Wang Department of Pediatric Dentistry Peking University School and Hospital of StomatologyBeijing 100081China State Key Laboratory of Natural and Biomimetic Drugs Chemical Biology Centerand School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Department of Prosthodontics Peking University School and Hospital of StomatologyBeijing 100081China

The effective management of bacterial infections that are resistant to multiple drugs remains a substantial clinical *** eradication of drug-resistant bacteria and subsequent promotion of angiogenesis are imperative for the regeneration of the infected ***,a novel and facile peptide containing injectable hydrogel with sustained antibacterial and angiogenic capabilities is *** antibacterial peptide that consists of 11 residues(CM11,WKLFKKILKVL)is loaded onto acrylate-modified gelatin through charge interactions.A vascular endothelial growth factor mimetic peptide KLT(KLTWQELYQLKYKGI)with a GCG(Gly-Cys-Gly)modification at the N-terminal is covalently coupled through a visible light-induced thiol-ene *** this reaction,the acrylate gelatin undergoes cross-linkage within *** on the physical/chemical double crosslinking strategy,the bioactive peptides achieve sustained and sequential *** results show that the hydrogel significantly inhibits methicillin-resistant Staphylococcus aureus(MRSA)growth through the rapid release of CM11 peptides at early stage;it forms obvious growth inhibition zones against pathogenic bacterial ***,cell counting kit-8 assay and scratch test confirm that the CM11/KLT-functionalized hydrogels promote cell proliferation and migration through the later release of KLT *** a mouse skin wound infected with self-luminous MRSA,the CM11/KLT-functionalized hydrogels enhance wound healing,with rapidly bacterial infection reduction,lower expression of inflammatory factors,and neovascularization *** results suggest that the rationally designed,sustained and sequential release CM11/KLT-functionalized hydrogels have huge potential in promoting the healing of multi-drug resistant bacterial infected wounds.

关键词： antimicrobial peptide vascular endothelial growth factor(VEGF)mimetic peptide sequential release visible-light crosslinking hydrogel wound therapy

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Recent advances in chemical protein synthesis:method developments and biological applications

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Science China Chemistry 2024年第4期67卷 1060-1096页

作者： suwei dong Ji-Shen Zheng Yiming Li Huan Wang Gong Chen Yongxiang Chen Gemin Fang Jun Guo Chunmao He Honggang Hu Xuechen Li Yanmei Li Zigang Li Man Pan Shan Tang Changlin Tian Ping Wang Bian Wu Chuanliu Wu Junfeng Zhao Lei Liu State Key Laboratory of Natural and Biomimetic Drugs and School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Division of Life Sciences and Medicine University of Science and Technology of ChinaHefei 230027China School of Food and Biological Engineering Engineering Research Center of Bio-processMinistry of EducationHefei University of TechnologyHefei 230009China School of Chemistry and Chemical Engineering Nanjing UniversityNanjing 210023China State Key Laboratory of Elemento-Organic Chemistry Nankai UniversityTianjin 300071China Department of Chemistry Tsinghua UniversityBeijing 100084China Institute of Health Sciences Anhui UniversityHefei 230601China College of Chemistry Central China Normal UniversityWuhan 430079China School of Chemistry and Chemical Engineering South China University of TechnologyGuangzhou 510640China School of Medicine or Institute of Translational Medicine Shanghai UniversityShanghai 200444China Department of Chemistry The University of Hong KongHong Kong 999077China Shenzhen Graduate School Peking UniversityShenzhen 518055China School of Chemistry and Chemical Engineering Shanghai Jiao Tong UniversityShanghai 200240China School of Life Sciences University of Science and Technology of ChinaHefei 230026China Department of Chemical Biology Shanghai Jiao Tong UniversityShanghai 200240China Institute of Microbiology Chinese Academy of SciencesBeijing 100101China Department of Chemistry Xiamen UniversityXiamen 361005China School of Pharmaceutical Science Guangzhou Medical UniversityGuangzhou 511436China

The central dogma of modern biology underscores the pivotal roles proteins play in diverse biological processes,the study of which necessitates advanced methods to produce proteins with precision and *** protein synthesis,a powerful approach utilizing chemical reactions for the de novo construction of structurally accurate proteins,has emerged as a transformative tool for studying proteins and generating protein derivatives/mimics inaccessible by natural biological machinery,including post-translationally modified proteins,proteins comprised of unnatural amino acids,as well as mirror-image *** review summarizes recent strides in synthetic method developments for chemical protein synthesis,including innovative techniques in solid-phase peptide synthesis,the challenges presented by difficult sequences in either synthesis or folding and the exploration of novel ligation reactions using both chemical and enzymatic ***,the review also delves into newly developed protocols for site-selective protein modifications and the generation of stapled or macrocyclized peptides/miniproteins,highlighting the power of chemical methods to make structurally diverse *** applications of synthetic proteins in investigating post-translational modifications(phosphorylation,lipidation,glycosylation,ubiquitination,etc.),mirror-image biological processes and drug development are further ***,these topics provide a comprehensive overview of the current landscape of chemical protein synthesis.

关键词： chemical protein synthesis solid-phase peptide synthesis ligation reactions post-translational modifications mirror-image proteins peptide drugs

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A citrullinated antigenic vaccine in treatment of autoimmune arthritis

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Science Bulletin 2024年第18期69卷 2920-2929页

作者： Xu Jin Tianya dong Qian Wang Yang Xie Xiangyu Fang Chaonan Wei Shuyan Liu Xi Zheng Ping Wang Danxue Zhu Lulu Cao suwei dong Kechi Fang Chao Zhong Jing Wang Fanlei Hu Zhanguo Li Department of Rheumatology and Immunology Peking University People’s Hospital&Beijing Key Laboratory for Rheumatism Mechanism and Immune DiagnosisBeijing 100044China Peking-Tsinghua Center for Life Sciences Peking UniversityBeijing 100871China CAS Key Laboratory of Mental Health Institute of PsychologyChinese Academy of SciencesBeijing 100101China Department of Psychology University of Chinese Academy of SciencesBeijing 100049China Department of Chemical Biology School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Institute of Systems Biomedicine Department of ImmunologyNHC Key Laboratory of Medical Immunology(Peking University)Beijing Key Laboratory of Tumor Systems BiologyPeking University Health Science CenterBeijing 100191China State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Department of Integration of Chinese and Western Medicine School of Basic Medical SciencesPeking UniversityBeijing 100191China

Rheumatoid arthritis(RA)is an inflammatory autoimmune disease triggered by antigenic peptides with environmental and genetic risk *** has been shown that antigen-specific targeting could be a promising therapeutical strategy for RA by restoring immune tolerance to self-antigens without compromising normal *** of antigens enhances antigenic properties and induces autoimmune ***,we showed that citrullinated antigenic(citAg)vaccine ameliorated collageninduced arthritis with decreased T-helper 1(Th1)and Th17 cells,downregulated proinflammatory cytokines including interlukin-6 and tumor necrosis factor-a,and inhibited antigen recall responses.B cell receptor sequencing further revealed that citAg vaccine could dampen the dysregulated V(D)J recombination,restoring the immune *** together,the results demonstrated that citAg vaccine might have a therapeutic effect on RA.

关键词： CitAg Citrullination Collagen typeⅡ Therapeutic vaccine Immune tolerance Rheumatoid arthritis

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Recent advances in the preparation of Fmoc-SPPS-based peptide thioester and its surrogates for NCL-type reactions

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Science China Chemistry 2017年第2期60卷 201-213页

作者： Hongxing Li suwei dong State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences Peking University Beijing 100191 China

Solid phase peptide synthesis(SPPS)based on Fmoc chemistry has become a commonly used technique in peptide chemistry,as it can be easily conducted using automated machine,and not requiring highly toxic HF in comparison to *** the fast development in the emerging field of protein chemical synthesis,many efforts have been endeavored aiming to find more efficient methods for preparing peptide fragments required in ligation *** review briefly summarizes recent advances in the engineering and modification of Fmoc-SPPS-derived peptides,which can be used as the N-terminal fragments in a native chemical ligation(NCL)or NCL-type ligation reactions.

关键词： native chemical ligation Fmoc-SPPS peptide thioester protein chemical synthesis

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Shape linear peptides into rigid rings: a sp^3 C–H arylation approach to cyclophane-braced peptide macrocycles

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Science China Chemistry 2018年第12期61卷 1477-1478页

作者： Yuankun Dao suwei dong State Key Laboratory of Natural and Biomimetic Drugs and Department of Chemical Biology School of Pharmaceutical SciencesPeking University

Peptide-based therapeutics have attracted increasing attention due to their unique properties in comparison to small molecule drugs and recombinant biologics [1].With moderate size and suitable surface area,peptides possess enormous potential in drug discovery for their promising capabilities of intercepting protein-protein interactions (PPIs),which is extremely difficult to be accomplished using small molecule compounds [2].

关键词： Shape linear peptides rigid rings peptide macrocycles

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Synthetic studies toward human interleukin-5

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Chinese Chemical Letters 2018年第7期29卷 1131-1134页

作者： Jinrong Liu suwei dong State Key Laboratory of Natural and Biomimetic Drugs Department of Chemical BiologySchool of Pharmaceutical SciencesPeking University

Interleukin 5(IL-5) is a human cytokine that regulates eosinophil growth and activation, and it plays essential roles in diseases associated with increased level of eosinophils such as asthma. Many studies have been conducted on this important glycoprotein, but all of them utilized recombinantly expressed samples. Here we describe our attempted chemical synthesis of IL-5, using protocols of Fmoc-SPPS and peptidyl hydrazide-based native chemical ligation, where the disulfide-reduced form of IL-5 is assembled from three peptide segments. Reconstitution of the protein under different folding conditions has also been investigated.

关键词： Interleukin 5 Eosinophilic disorders Asthma Solid phase peptide synthesis Native chemical ligation Mirror-image phage display

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Facile Generation of Strained Peptidyl Thiolactones from Hydrazides and Its Application in Assembling MUC-1 VNTR OIigomers

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Chinese Journal of Chemistry 2021年第9期39卷 2509-2516页

作者： Yuankun Dao Biao Wang Weidong dong Jun Zhang Chao Zhong Zhili Zhang suwei dong State Key Laboratory of Natural and Biomimetic Drugs and Department of Chemical BiologySchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China Institute of Systems Biomedicine School of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China

An efficient method for the activation of C-terminal 4-mecaptoproline-or penicillamine-containing peptide hydrazides in ligation re-actions is reported *** corresp on ding peptide hydrazides can be readily prepared using solid-phase peptide synthesis,and subsequently activated by acetylacet one(acac)without exoge nous thiol *** peptidyl thiolactones could be the possible reactive in termediates that drastically accelerate the reacti on rates at the sterically demandi ng proline and valine *** developed protocol allows for sequential peptide ligations in a one-pot manner,and expedites the assembly of mucin 1(MUC-1)variable number tandem repeat(VNTR)trimers in various glycosylated forms.

关键词： Strained molecules Glycopeptides Synthetic methods Peptidyl thiolactones

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Mutual interaction of microbiota and host immunity during health and diseases

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Biophysics Reports 2021年第4期7卷 326-340页

作者： Di Wu Yinlian Zhang suwei dong Chao Zhong Institute of Systems Biomedicine Department of ImmunologyBeijing Key Laboratory of Tumor Systems BiologyPeking University Health Science Center State Key Laboratory of Natural and Biomimetic Drugs Department of Chemical BiologySchool of Pharmaceutical SciencesPeking University

Microbiota–host interaction has attracted more and more attentions in recent years. The association between microbiota and host health is largely attributed to its influence on host immune ***-derived antigens and metabolites play a critical role in shaping the host immune system,including regulating its development, activation, and function. However, during various diseases the microbiota–host communication is frequently found to be disordered. In particular, gut microbiota dysbiosis associated with or led to the occurrence and progression of infectious diseases, autoimmune diseases, metabolic diseases, and neurological diseases. Pathogenic microbes and their metabolites disturb the protective function of immune system, and lead to disordered immune responses that usually correlate with disease exacerbation. In the other hand, the immune system also regulates microbiota composition to keep host homeostasis. Here, we will discuss the current advances of our knowledge about the interactions between microbiota and host immune system during health and diseases.

关键词： Microbiota Microbial-derived antigens and metabolites Immune system Composition of microbiota Host health and diseases

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Synthesis and biological evaluation of a lipopeptide-based methamphetamine vaccine

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Chinese Chemical Letters 2021年第4期32卷 1575-1579页

作者： Fan Liao Hanxuan Wang Yuankun Dao Kai Yuan Jiazhen Lu Jie Shi Ying Han suwei dong Lin Lu Peking University Sixth Hospital Peking University Institute of Mental HealthNHC Key Laboratory of Mental Health(Peking University)National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital)Beijing 100191China National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence Peking UniversityBeijing 100191China State Key Laboratory of Natural and Biomimetic Drugs and Department of Chemical BiologySchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovem Institute for Brain Research Academy for Advanced Interdisciplinary Studies Peking UniversityBeijing 100871China School of Basic Medicine Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

We describe an application of carrier protein-free strategy in constructing a fully synthetic methamphetamine(METH)vaccine that contains three components:Toll-like receptor 2 ligand,Th2 epitope,and METH *** immunological evaluation in mice revealed high titers of METH-specific antibodies induced by the construct and the activation of humoral immunity that would be beneficial for neutralization and clearance of the METH *** ral experiments indicated that the synthetic vaccine attenuated the acquisition of METH-induced conditioned place preference and inhibited the initiation and expression of METH-induced locomotor *** results demonstrate that the lipopeptide-based vaccine has invo ked an immune response and showed the potential of preventing the rewarding and psychoactive effects of METH.

关键词： METH vaccine Carrier protein-free Fully synthesis Lipopeptide Behavioral model

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Protection-Free Site-Directed Peptide or Protein S-Glycosylation and Its Application in the Glycosylation of Glucagon-like Peptide 1

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CCS Chemistry 2022年第6期4卷 1930-1937页

作者： Gefei Li Yuankun Dao Juan Mo suwei dong Shin-ichiro Shoda Xin-Shan Ye State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191 Department of Biomolecular Engineering Graduate School of EngineeringTohoku UniversityAoba-kuSendai 980-8579

The development of a facile cysteine-directed S-glycosylation strategy would facilitate the intensive investigation of the effect of glycosylation on protein translational ***,we introduce glycosyl Bunte salt as an efficient glycosyl donor for site-selective peptide/protein *** coupling reaction with cysteine thiols under alkaline buffer conditions proceeded chemoselectively,delivering homogeneous glycoconjugates and inorganic salt as the only byproduct.A series of sugar moieties,including monosaccharides and oligosaccharides,were successfully conjugated to the peptides and protein via the disulfide ***,this protocol was applied to the glycosylation of the glucagon-like peptide 1(GLP-1)variant,and its glycosylated effect on blood glucose control was also studied.

关键词： site-selective S-glycosylation peptide/protein-modification glycosyl Bunte salt disulfide bond GLP-1

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