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模拟宿主防御肽的聚(2-噁唑啉)作为佐剂增强多粘菌素B的抗菌活性并拓展抗菌谱

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Science China Materials 2024年第3期67卷 991-999页

作者：罗政杰赵学斌周敏邹景橙肖希勉刘龙强谢佳洋武月铭张雯静刘润辉 State Key Laboratory of Bioreactor Engineering East China University of Science and TechnologyShanghai 200237China Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism Key Laboratory for Ultrafine Materials of Ministry of EducationFrontiers Science Center for Materiobiology and Dynamic ChemistryResearch Center for Biomedical Materials of Ministry of EducationSchool of Materials Science and EngineeringEast China University of Science and TechnologyShanghai 200237China Department of Orthopedic Surgery Shanghai General HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200080China

临床上常用的广谱抗生素无法有效解决抗生素高度耐药ESKAPE菌感染的难题,ESKAPE耐药菌已经成为人类生命健康的重大威胁.抗生素与佐剂的联合治疗是解决抗生素耐药菌感染的重要途径,但是探索对所有ESKAPE耐药菌都具有广谱和高效抗菌活性... 详细信息

临床上常用的广谱抗生素无法有效解决抗生素高度耐药ESKAPE菌感染的难题,ESKAPE耐药菌已经成为人类生命健康的重大威胁.抗生素与佐剂的联合治疗是解决抗生素耐药菌感染的重要途径,但是探索对所有ESKAPE耐药菌都具有广谱和高效抗菌活性的抗生素-佐剂组合仍然面临巨大挑战.在这里,我们提出了一种抗生素-佐剂的有效设计策略,将对ESKAPE中耐药阴性菌具有高活性的多粘菌素B(PMB)与模拟宿主防御肽的细菌膜靶向阳离子聚(2-噁唑啉)相结合.我们通过2-噁唑啉单体可控聚合,合成了一系列具有不同疏水性侧链的阳离子聚(2-噁唑啉).研究表明,聚(2-噁唑啉)和PMB的组合效果随着聚(2-噁唑啉)侧链疏水性的提高呈现出从拮抗效应到协同效应的逐渐变化.其中,优选的聚(2-噁唑啉)EACA-POX_(20)显著增强了PMB的抗菌活性,尤其是对于ESKAPE耐药阳性菌的抗菌活性增强了16–32倍.聚(2-噁唑啉)EACA-POX_(20)有效增强了PMB的抗菌活性并扩展了PMB的抗菌谱.聚(2-噁唑啉)和PMB的组合策略能够有效对抗所有耐药ESKAPE病原体,为解决ESKAPE耐药菌提供了新的思路.

关键词： poly(2-oxazoline)s ESKAPE bacteria polymyxin B broad-spectrum activity

In vitro and in vivo evaluation of implantable bacterial-killing coatings based on host defense peptides and their synthetic mimics

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Journal of Materials Science & Technology 2021年第32期91卷 90-104页

作者： Yuxin Qian Shuai Deng Xue Wu Yunrui She runhui liu Haodong Lin State Key Laboratory of Bioreactor Engineering East China University of Science and TechnologyShanghai 200237China Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic ChemistryResearch Center for Biomedical Materials of Ministry of EducationSchool of Materials Science and EngineeringEast China University of Science and TechnologyShanghai 200237China Department of Orthopedic Surgery Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China

Contact-killing antimicrobial coatings based on host defense peptides(HDPs) and their synthetic mimics have shown potential as powerful tools to combat implant-associated infections. Covalent modification of the antimicrobial surface has been utilized to prevent early-stage microbial infections owing to the less drug-leaching possibility that is beneficial to human health and the natural environment. Although considerable progress has been achieved in preparing contact-killing antimicrobial surfaces, discussions focusing on the in vitro and in vivo evaluations of these surfaces are limited. In this review, we summarized the established in vitro methods to simulate the practical interaction of microbes with the surrounding biological environment and the reported in vivo studies at different implant sites. We suggested that the in vivo specific site infection model is essential to gain a comprehensive understanding of these antimicrobial coatings in the preclinical stage, which can be established based on investigations performed using various in vitro assays and conventional non-specific site infection models. Overall, these precedent studies focusing on bacterial contact-killing coatings modified with HDPs and HDP mimics can be considered as critical to assess the surface antibacterial ability and to guide the future developments and applications of antimicrobial surfaces.

关键词： Contact-killing Antimicrobial surface HDPs HDP mimic Covalent binding

Dual Functional Diblock Amino Acid Copolymer Displaying Synergistic Effect with Curcumin against MRSA and Encapsulation of Curcumin

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Chinese Journal of Chemistry 2023年第23期41卷 3333-3338页

作者： Yueming Wu Yuan Chen Haowen Yu Alideertu Dong runhui liu State Key Laboratory of Bioreactor Engineering East China University of Science and TechnologyShanghai200237 China Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic Chemistry Shanghai Frontiers Science Center of Optogenetic Techniques for Cell MetabolismResearch Center for Biomedical Materials of Ministry of EducationSchool of Materials Science and EngineeringEast China University of Science and TechnologyShanghai200237 China Engineering Research Center of Dairy Quality and Safety Control Technology Ministry of EducationInner Mongolia UniversityHohhotInner Mongolia010021 China

The intensive use of antibiotics intensifies the development of bacterial resistance,which has become a serious problem ***-resistant Staphylococcus aureus(MRSA)has resulted in significant morbidity and ***,it is an urgent need to develop new antimicrobial drugs and administration ***,we report a dual functional diblock copolymer PLL20-b-PBLG20,which was prepared by superfast and water-insensitive polymerization on N-carboxyanhydrides(NCA)initiated by tetraalkylammonium *** addition to direct antimicrobial activity,PLL20-b-PBLG20 also exerts a synergistic bactericidal effect against MRSA with curcumin,a plant extract with antibacterial ***,PLL20-b-PBLG20 successfully encapsulates curcumin to form nanoparticles via *** combination of dual functional PLL20-b-PBLG20 and curcumin holds promise in combating MRSA infections.

关键词： Amino acid polymer Antimicrobial Synergy Encapsulation MRSA

麝香保心丸“异病同治”2型糖尿病和冠心病的网络药理学作用机制研究

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药学实践与服务 2024年第4期42卷 173-180页

作者：朱子凡王智聪谢彬柳润辉福建中医药大学福建福州350122 海军军医大学药学系上海200433

目的基于网络药理学方法研究麝香保心丸“异病同治”2型糖尿病(T2DM)和冠心病(CHD)的作用机制。方法运用中药系统药理学数据库与分析平台(TCMSP)、中药成分数据库(TCMID)、中医药百科全书数据库(ETCM)和BATMAN-TCM数据库筛选麝香保心... 详细信息

目的基于网络药理学方法研究麝香保心丸“异病同治”2型糖尿病(T2DM)和冠心病(CHD)的作用机制。方法运用中药系统药理学数据库与分析平台(TCMSP)、中药成分数据库(TCMID)、中医药百科全书数据库(ETCM)和BATMAN-TCM数据库筛选麝香保心丸中七味中药的化学成分和作用靶点,利用DisGeNET和GeneCards数据库获取与CHD和T2DM相关的疾病靶点。运用Cytoscape3.8.2软件构建“药物-成分-靶点”网络图,利用STRING数据库构建蛋白互作(PPI)网络图,利用DAVID在线数据库对麝香保心丸治疗T2DM和CHD的共同作用靶点进行GO生物过程分析和KEGG通路富集分析。结果共筛选出麝香保心丸治疗T2DM和CHD的潜在活性成分101个,对应229个靶点。网络分析结果表明,麝香保心丸治疗T2DM和CHD的共同主要成分可能是鹅去氧胆酸、熊去氧胆酸、肉桂醛、胆汁酸、肉桂酸及人参皂苷类成分。通路富集分析结果显示,麝香保心丸“异病同治”T2DM和CHD的作用机制可能与抑制炎症反应和氧化应激有关。结论麝香保心丸可通过多成分、多靶点、多途径发挥“异病同治”T2DM和CHD的作用,为麝香保心丸的临床应用及进一步研究提供理论基础。

关键词：麝香保心丸 2型糖尿病冠心病异病同治网络药理学

Synergistic Combination of Biodegradable Peptide Polymer and Curcumin as Promising Antibiotic Substitution in Aquaculture to Alleviate the Global Challenge of Antimicrobial Resistance

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Chinese Journal of Chemistry 2022年第24期40卷 2947-2955页

作者： Pengcheng Ma Yuan Chen Ning Shao Junyu Zhang Yueming Wu runhui liu State Key Laboratory of Bioreactor Engineering East China University of Science and TechnologyShanghai200237 China Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic ChemistryShanghai Frontiers Science Center of Optogenetic Techniques for Cell MetabolismResearch Center for Biomedical Materials of Ministry of EducationSchool of Materials Science and EngineeringEast China University of Science and TechnologyShanghai200237 China

The massive use of antibiotics in aquaculture and resulted antibacterial resistance problem urgently need antibiotic substitutions. Herein, we report a promising substitution of aquaculture antibiotics using a synergistic combination of biodegradable peptide polymers and curcumin, a natural compound from plant. The synergistic combination shows strong antibacterial activity against V. fluvialis and some other common bacteria in aquaculture. The membrane-damaging antibacterial mechanism echoes our finding that the synergistic combination will not induce bacteria to develop resistance after continuous use. The synergistic combination also displays effective cure on V. fluvialis-infected zebrafish. The biodegradability of the peptide polymer enables the combination to lose antibacterial activity and will not cause selective pressure on bacterial in the environment. Our study indicates potential application of synergistic composition, biodegradable peptide polymer and curcumin, as promising antibiotic substitution in aquaculture, which represents a promising strategy to address the global challenge of antimicrobial resistance.

关键词： Antimicrobial polymer Aquaculture Peptides Antibiotics Biological activity

Host defense peptide-mimickingβ-peptide polymer displaying strong antibacterial activity against cariogenic Streptococcus mutans

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Journal of Materials Science & Technology 2023年第2期133卷 77-88页

作者： Yi Yang Yuxin Qian Mingxing Zhang Shuang Hao Hui Wang Yongqiang Fan runhui liu Dake Xu Fuhui Wang Life and Health Sciences Northeastern UniversityShenyang 110819China Shenyang National Laboratory for Materials Science Northeastern UniversityShenyang 110819China Electrobiomaterials Institute Key Laboratory for Anisotropy and Texture of MaterialsMinistry of EducationNortheastern UniversityShenyang 110819China State Key Laboratory of Bioreactor Engineering East China University of Science and TechnologyShanghai 200237China School of Environmental and Safety Engineering Liaoning Petrochemical UniversityFushun 113001China Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic ChemistryResearch Center for Biomedical Materials of Ministry of EducationSchool of Materials Science and EngineeringEast China University of Science and TechnologyShanghai 200237China

Cariogenic Streptococcus mutans(***)is a leading cause of bacterial-induced oral *** strategies to kill bacteria based on Host defense peptide(HDP)mimicking polymers hold promise to treat oral bacterial ***,we explore the impact of hydrophobic subunit and chain length variation on the antibacterial and antibiofilm activity ofβ-peptide *** physicochemical and biological prop-erties,such as the toxicity,the antibacterial activity,and the effect on bacterial transcription ofβ-peptide polymers,were systematically investigated with numerous *** results exhibited that the op-timalβ-peptide polymer has low toxicity towards human periodontal ligament fibroblasts,andβ-peptide polymers(especially P3)have more excellent antibacterial activity against *** than *** addition,β-peptide polymers inhibited the reversible and irreversible bacterial adhesion during the formation of *** polymer can promote biofilm dispersion by decreasing the hydrophobicity of bacterial cells after adhering to cell *** of the transcriptome for *** treated withβ-peptide polymers demonstrated thatβ-peptide polymers could reduce the cariogenicity of *** by impacting the transcription of the energy and acid metabolism-related genes.β-peptide polymers are promising antimicrobial agents in clinical dentistry due to their high antibacterial efficiency and low tox-icity.

关键词： β-peptide polymers Host defense peptide S.mutans RT-qPCR Transcriptome

Alkali-metal hexamethyldisilazide initiated polymerization on alpha-amino acid N-substituted N-carboxyanhydrides for facile polypeptoid synthesis

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Chinese Chemical Letters 2021年第5期32卷 1675-1678页

作者： Yueming Wu Min Zhou Kang Chen Sheng Chen Ximian Xiao Zhemin Ji Jingcheng Zou runhui liu State Key Laboratory of Bioreactor Engineering East China University of Science and TechnologyShanghai 200237China Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic ChemistryResearch Center for Biomedical Materials of Ministry of EducationSchool of Materials Science and EngineeringEast China University of Science and TechnologyShanghai 200237China

Polypeptoids have been explored as mimics of polypeptides,owing to polypeptoids'superior stability upon *** can be synthesized from one-pot ring-opening polymerization of amino acid N-substituted N-carboxyanhydrides(NNCAs).However,the speed of polymerization of NNCAs can be very slow,especially for NNCAs bearing a bulky N-substitution *** hindered the exploration on polypeptoids with more diverse structures and ***,it is in great need to develop advanced strategies that can accelerate the polymerization on inactive ***,we report that lithium/sodium/potassium hexamethyldisilazide(Li/Na/KHMDS)initiates a substantially faster polymerization on NNCAs than do commonly used amine initiators,especially for NNCAs with bulky N-substitution *** fast NNCA polymerization will increase the structure diversity and application of polypeptoids as synthetic mimics of polypeptides.

关键词： Polypeptoids Peptide mimics N-Substituted N-carboxyanhydrides(NNCA) Lithium hexamethyldisilazide Sodium hexamethyldisilazide Potassium hexamethyldisilazide Ring-opening polymerization Inactive NNCA

Breaking or following the membrane-targeting mechanism:Exploring the antibacterial mechanism of host defense peptide mimicking poly(2-oxazoline)s

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Journal of Materials Science & Technology 2020年第24期59卷 220-226页

作者： Chengzhi Dai Min Zhou Weinan Jiang Ximian Xiao Jingcheng Zou Yuxin Qian Zihao Cong Zhemin Ji Longqiang liu Jiayang Xie Zhongqian Qiao runhui liu State Key Laboratory of Bioreactor Engineering Frontiers Science Center for Materiobiology and Dynamic ChemistryKey Laboratory of Specially Functional Polymeric Materials and Related Technology(ECUST)Ministry of EducationSchool of Materials Science and EngineeringEast China University of Science and TechnologyShanghai200237China State Key Laboratory of Molecular Engineering of Polymers(Fudan University) Shanghai200438China

Peptides exert important biological functions but their application is hindered by their susceptibility to proteolysis and poor stability in ***,functional peptide mimics have drawn a great deal of attention to address this ***(2-oxazoline)s,a class of biocompatible and proteolysis-resistant polymer,can work as host defense peptide mimics without following the general membrane-targeting mechanism as shown in our previous *** observation encouraged us to figure out if poly(2-oxazoline)s are special and break the general membrane-targeting mechanism of host defense peptides and their *** this study,we aimed at the connection between structure and antibacterial mechanism of poly(2-oxazoline)s.A new γ-aminobutyric acid(GABA)-pendent poly(2-oxazoline)was synthesized and investigated to compare with glycine-pendent poly(2-oxazoline)in our previous study,with the former polymer has two extra CH2 groups in the sidechain to increase the hydrophobicity and *** depolarization assay suggested that incorporating two more CH2 groups into the sidechain of poly(2-oxazoline)resulted in a mechanism switch from DNA-targeting to membrane-targeting,which was supported by the slow time-kill kinetics and slightly distorted and sunken membrane ***,GABA-pendent poly(2-oxazoline)showed potent activity against methicillin-resistant *** and low hemolysis on human red blood ***,repeated use of the antimicrobial poly(2-oxazoline)did not stimulate bacteria to obtain resistance,which was an obvious advantage of membrane-targeting antimicrobial agents.

关键词： Poly(2-oxazoline) Host defense peptide Antibacterial mechanism Membrane-targeting Antimicrobial resistance

Host defense peptide-mimicking peptide polymer-based antibacterial hydrogel enables efficient healing of MRSA-infected wounds

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Science China Chemistry 2023年第6期66卷 1824-1833页

作者： Zhongqian Qiao Wenjing Zhang Yueming Wu Weinan Jiang Ning Shao Jiayang Xie Guixue Xia Qimeng Chen Zhefeng liu Jingcheng Zou Jiawei Gu Shifang Luan Haodong Lin runhui liu State Key Laboratory of Bioreactor Engineering East China University of Science and TechnologyShanghai 200237China Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic ChemistryShanghai Frontiers Science Center of Optogenetic Techniques for Cell MetabolismResearch Center for Biomedical Materials of Ministry of EducationSchool of Materials Science and EngineeringEast China University of Science and TechnologyShanghai 200237China Department of Orthopedic Surgery Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China State Key Laboratory of Polymer Physics and Chemistry Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China

Wound infections are a compelling health issue caused by the invasion and proliferation of pathogens in wound *** hydrogels are widely used to achieve anti-infectious wound ***,due to the quick emergence of drugresistant bacteria,such as methicillin-resistant Staphylococcus aureus(MRSA),wound infection has been a formidable challenge to human *** address MRSA-infected wounds,an antibacterial peptide polymer-loaded hyaluronic acid(HA)hydrogel(Gel-HA@P)is *** peptide polymer is designed to mimic host defense peptides as the antibiotic alternative showing potent antibacterial activity,low susceptibility to drug resistance and good stability against *** is biocompatible and biodegradable hydrogel substrate as a primary constituent of the extracellular matrix and suitable for cell migration and wound ***-HA@P shows potent activity against MRSA in vitro and in vivo,low toxicity during the treatment and promotes the wound healing in *** design has proven to be an effective and antibiotic-free strategy to enable the healing of MRSA-infected wounds.

关键词： peptide polymer wound healing MRSA drug-resistance host defense peptide