具有高效抗MRSA活性的Alpha-Beta杂化多肽聚合物分子刷（英文）
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摘要
近年来,以耐甲氧西林金黄色葡萄球菌(MRSA)为代表的"超级细菌"不断被发现和扩散,已经严重威胁人类健康,因此,研制新型、高效的抗菌剂迫在眉睫.以宿主防御肽及其模拟物为代表的多肽和聚合物近年来得到广泛关注.而分子刷作为一类独特的聚合物也显示了很多特殊的性能.我们结合前期研究,首次将两种开环聚合体系即β-内酰胺开环聚合和N-羧基环内酸酐(NCA)开环聚合体系相结合,以β多肽为骨架结构进而通过其氨基功能基团进一步引发NCA开环聚合,合成了侧链具有多个聚赖氨酸的α/β杂化多肽聚合物分子刷.这种新型分子刷对多种MRSA菌株均展现出高效的抗菌活性,甚至优于万古霉素.通过扫描电子显微镜(SEM)表征,揭示了α/β杂化多肽聚合物分子刷的抗菌机理与宿主防御肽类似,是通过破坏细菌细胞膜的完整性杀菌.α/β杂化多肽聚合物分子刷高度可调的结构特点和高效的抗菌活性,显示了其在抗菌研究和应用中的潜力.
引文
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9 Hu D,Li H,Wang B,et al.Surface-adaptive gold nanoparticles with effective adherence and enhanced photothermal ablation of methicillin-resistant Staphylococcus aureus biofilm.ACS Nano,2017,11:9330-9339
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11 Wei T,Tang Z,Yu Q,et al.Smart antibacterial surfaces with switchable bacteria-killing and bacteria-releasing capabilities.ACSAppl Mater Interfaces,2017,9:37511-37523
12 Hancock REW,Haney EF,Gill EE.The immunology of host defence peptides:Beyond antimicrobial activity.Nat Rev Immunol,2016,16:321-334
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18 Palermo EF,Sovadinova I,Kuroda K.Structural determinants of antimicrobial activity and biocompatibility in membrane-disrupting methacrylamide random copolymers.Biomacromolecules,2009,10:3098-3107
19 Jiang Y,Yang X,Zhu R,et al.Acid-activated antimicrobial random copolymers:A mechanism-guided design of antimicrobial peptide mimics.Macromolecules,2013,46:3959-3964
20 Xiong M,Lee MW,Mansbach RA,et al.Helical antimicrobial polypeptides with radial amphiphilicity.Proc Natl Acad Sci USA,2015,112:13155-13160
21 Qian Y,Zhang D,Wu Y,et al.The design,synthesis and biological activity study of nylon-3 polymers as mimics of host defense peptides.Acta Polym Sin,2016,1300-1311
22 Liu R,Suárez JM,Weisblum B,et al.Synthetic polymers active against Clostridium difficile vegetative cell growth and spore outgrowth.J Am Chem Soc,2014,136:14498-14504
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24 Liu R,Chen X,Falk SP,et al.Nylon-3 polymers active against drug-resistant Candida albicans biofilms.J Am Chem Soc,2015,137:2183-2186
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29 Niu Y,Padhee S,Wu H,et al.Lipo-γ-AApeptides as a new class of potent and broad-spectrum antimicrobial agents.J Med Chem,2012,55:4003-4009
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31 Yarlagadda V,Akkapeddi P,Manjunath GB,et al.Membrane active vancomycin analogues:A strategy to combat bacterial resistance.J Med Chem,2014,57:4558-4568
32 Yarlagadda V,Samaddar S,Paramanandham K,et al.Membrane disruption and enhanced inhibition of cell-wall biosynthesis:Asynergistic approach to tackle vancomycin-resistant bacteria.Angew Chem Int Ed,2015,54:13644-13649
33 Choi H,Chakraborty S,Liu R,et al.Single-cell,time-resolved antimicrobial effects of a highly cationic,random nylon-3 copolymer on live Escherichia coli.ACS Chem Biol,2016,11:113-120
34 Ding X,Duan S,Ding X,et al.Versatile antibacterial materials:An emerging arsenal for combatting bacterial pathogens.Adv Funct Mater,2018,362:1802140
35 Su Y,Tian L,Yu M,et al.Cationic peptidopolysaccharides synthesized by‘click’chemistry with enhanced broad-spectrum antimicrobial activities.Polym Chem,2017,8:3788-3800
36 Pranantyo D,Xu LQ,Hou Z,et al.Increasing bacterial affinity and cytocompatibility with four-arm star glycopolymers and antimicrobialα-polylysine.Polym Chem,2017,8:3364-3373
37 Lu H,Wang J,Lin Y,et al.One-pot synthesis of brush-like polymers via integrated ring-opening metathesis polymerization and polymerization of amino acid N-carboxyanhydrides.J Am Chem Soc,2009,131:13582-13583
38 Wang J,Lu H,Ren Y,et al.Interrupted helical structure of grafted polypeptides in brush-like macromolecules.Macromolecules,2015,44:8699-8708
39 Meereboer NL,Terzi?I,Saidi S,et al.Two-dimensional controlled syntheses of polypeptide molecular brushes via N-carboxyanhydride ring-opening polymerization and ring-opening metathesis polymerization.ACS Macro Lett,2017,6:1031-1035
40 Beers KL,Gaynor SG,Matyjaszewski K,et al.The synthesis of densely grafted copolymers by atom transfer radical polymerization.Macromolecules,1998,31:9413-9415
41 Cheng G,B?ker A,Zhang M,et al.Amphiphilic cylindrical core-shell brushes via a“grafting from”process using atrp.Macromolecules,2001,34:6883-6888
42 Gerle M,Fischer K,Roos S,et al.Main chain conformation and anomalous elution behavior of cylindrical brushes as revealed by GPC/MALLS,light scattering,and SFM.Macromolecules,1999,32:2629-2637
43 Li Z,Ma J,Cheng C,et al.Synthesis of hetero-grafted amphiphilic diblock molecular brushes and their self-assembly in aqueous medium.Macromolecules,2010,43:1182-1184
44 Müllner M,Dodds SJ,Nguyen TH,et al.Size and rigidity of cylindrical polymer brushes dictate long circulating properties in vivo.ACS Nano,2015,9:1294-1304
45 Neugebauer D,Sumerlin BS,Matyjaszewski K,et al.How dense are cylindrical brushes grafted from a multifunctional macroinitiator?Polymer,2004,45:8173-8179
46 Runge MB,Bowden NB.Synthesis of high molecular weight comb block copolymers and their assembly into ordered morphologies in the solid state.J Am Chem Soc,2007,129:10551-10560
47 Xia Y,Kornfield JA,Grubbs RH.Efficient synthesis of narrowly dispersed brush polymers via living ring-opening metathesis polymerization of macromonomers.Macromolecules,2009,42:3761-3766
48 Zheng G,Pan C.Reversible addition-fragmentation transfer polymerization in nanosized micelles formed in situ.Macromolecules,2006,39:95-102
49 Xia Y,Olsen BD,Kornfield JA,et al.Efficient synthesis of narrowly dispersed brush copolymers and study of their assemblies:The importance of side chain arrangement.J Am Chem Soc,2009,131:18525-18532
50 Zhang Y,Yin Q,Lu H,et al.Peg-polypeptide dual brush block copolymers:Synthesis and application in nanoparticle surface pegylation.ACS Macro Lett,2013,2:809-813
51 Gao Q,Yu M,Su Y,et al.Rationally designed dual functional block copolymers for bottlebrush-like coatings:In vitro and in vivo antimicrobial,antibiofilm,and antifouling properties.Acta Biomater,2017,51:112-124
52 Verduzco R,Li X,Pesek SL,et al.Structure,function,self-assembly,and applications of bottlebrush copolymers.Chem Soc Rev,2015,44:2405-2420
53 Lu X,Tran TH,Jia F,et al.Providing oligonucleotides with steric selectivity by brush-polymer-assisted compaction.J Am Chem Soc,2015,137:12466-12469
54 Gao AX,Liao L,Johnson JA.Synthesis of acid-labile peg and pegdoxorubicin-conjugate nanoparticles via brush-first romp.ACSMacro Lett,2014,3:854-857
55 Gao H,Matyjaszewski K.Synthesis of molecular brushes by“grafting onto”method:combination of ATRP and click reactions.J Am Chem Soc,2007,129:6633-6639
56 Guo J,Hong H,Chen G,et al.Theranostic unimolecular micelles based on brush-shaped amphiphilic block copolymers for tumortargeted drug delivery and positron emission tomography imaging.ACS Appl Mater Interfaces,2014,6:21769-21779
57 H?rtz C,Birke A,Kaps L,et al.Cylindrical brush polymers with polysarcosine side chains:A novel biocompatible carrier for biomedical applications.Macromolecules,2015,48:2074-2086
58 Jin X,Sun P,Tong G,et al.Star polymer-based unimolecular micelles and their application in bio-imaging and diagnosis.Biomaterials,2018,178:738-750
59 Li H,Liu H,Nie T,et al.Molecular bottlebrush as a unimolecular vehicle with tunable shape for photothermal cancer therapy.Biomaterials,2018,178:620-629
60 Liao L,Liu J,Dreaden EC,et al.A convergent synthetic platform for single-nanoparticle combination cancer therapy:Ratiometric loading and controlled release of cisplatin,doxorubicin,and camptothecin.J Am Chem Soc,2014,136:5896-5899
61 Müllner M,Mehta D,Nowell CJ,et al.Passive tumour targeting and extravasation of cylindrical polymer brushes in mouse xenografts.Chem Commun,2016,52:9121-9124
62 Sowers MA,McCombs JR,Wang Y,et al.Redox-responsive branched-bottlebrush polymers for in vivo MRI and fluorescence imaging.Nat Commun,2014,5:5460
63 von Erlach T,Zwicker S,Pidhatika B,et al.Formation and characterization of DNA-polymer-condensates based on poly(2-methyl-2-oxazoline)grafted poly(l-lysine)for non-viral delivery of therapeutic DNA.Biomaterials,2011,32:5291-5303
64 Zeng X,Wang L,Liu D,et al.Poly(l-lysine)-based cylindrical copolypeptide brushes as potential drug and gene carriers.Colloid Polym Sci,2016,294:1909-1920
65 Liu R,Masters KS,Gellman SH.Polymer chain length effects on fibroblast attachment on nylon-3-modified surfaces.Biomacromolecules,2012,13:1100-1105
66 Liu R,Chen X,Gellman SH,et al.Nylon-3 polymers that enable selective culture of endothelial cells.J Am Chem Soc,2013,135:16296-16299
67 Liu R,Chen X,Falk SP,et al.Structure-activity relationships among antifungal nylon-3 polymers:identification of materials active against drug-resistant strains of Candida albicans.J Am Chem Soc,2014,136:4333-4342
68 Hou Y,Wang Y,Wang R,et al.Harnessing phosphato-platinum bonding induced supramolecular assembly for systemic cisplatin delivery.ACS Appl Mater Interfaces,2017,9:17757-17768
69 Qian Y,Qi F,Chen Q,et al.Surface modified with a host defense peptide-mimickingΒ-peptide polymer kills bacteria on contact with high efficacy.ACS Appl Mater Interfaces,2018,10:15395-15400
70 Chakraborty S,Liu R,Hayouka Z,et al.Ternary nylon-3 copolymers as host-defense peptide mimics:Beyond hydrophobic and cationic subunits.J Am Chem Soc,2014,136:14530-14535
71 Zhang D,Zhang S,Ma P,et al.Synthetic peptidyl polymer displaying potent activity against gram positive bacteria.J Funct Polym,2018,DOI:10.14133/j.cnki.1008-9357.20180410001
72 Hovakeemian SG,Liu R,Gellman SH,et al.Correlating antimicrobial activity and model membrane leakage induced by nylon-3 polymers and detergents.Soft Matter,2015,11:6840-6851
2 Purrello SM,Garau J,Giamarellos E,et al.Methicillin-resistant Staphylococcus aureus infections:A review of the currently available treatment options.J Glob Antimicrobial Resistance,2016,7:178-186
3 Hancock REW,Sahl HG.Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies.Nat Biotechnol,2006,24:1551-1557
4 Boman HG.Antibacterial peptides:Basic facts and emerging concepts.J Intern Med,2003,254:197-215
5 Zasloff M.Antimicrobial peptides of multicellular organisms.Nature,2002,415:389-395
6 Nederberg F,Zhang Y,Tan JPK,et al.Biodegradable nanostructures with selective lysis of microbial membranes.Nat Chem,2011,3:409-414
7 Bai H,Yuan H,Nie C,et al.A supramolecular antibiotic switch for antibacterial regulation.Angew Chem Int Ed,2015,54:13208-13213
8 Liu K,Liu Y,Yao Y,et al.Supramolecular photosensitizers with enhanced antibacterial efficiency.Angew Chem Int Ed,2013,52:8285-8289
9 Hu D,Li H,Wang B,et al.Surface-adaptive gold nanoparticles with effective adherence and enhanced photothermal ablation of methicillin-resistant Staphylococcus aureus biofilm.ACS Nano,2017,11:9330-9339
10 Huang Y,Ding X,Qi Y,et al.Reduction-responsive multifunctional hyperbranched polyaminoglycosides with excellent antibacterial activity,biocompatibility and gene transfection capability.Biomaterials,2016,106:134-143
11 Wei T,Tang Z,Yu Q,et al.Smart antibacterial surfaces with switchable bacteria-killing and bacteria-releasing capabilities.ACSAppl Mater Interfaces,2017,9:37511-37523
12 Hancock REW,Haney EF,Gill EE.The immunology of host defence peptides:Beyond antimicrobial activity.Nat Rev Immunol,2016,16:321-334
13 Yang Y,He P,Wang Y,et al.Supramolecular radical anions triggered by bacteria in situ for selective photothermal therapy.Angew Chem Int Ed,2017,56:16239-16242
14 Porter EA,Wang X,Lee HS,et al.Non-haemolyticβ-amino-acid oligomers.Nature,2000,404:565
15 Kuroda K,DeGrado WF.Amphiphilic polymethacrylate derivatives as antimicrobial agents.J Am Chem Soc,2005,127:4128-4129
16 Lienkamp K,Madkour AE,Musante A,et al.Antimicrobial polymers prepared by romp with unprecedented selectivity:Amolecular construction kit approach.J Am Chem Soc,2008,130:9836-9843
17 Song A,Walker SG,Parker KA,et al.Antibacterial studies of cationic polymers with alternating,random,and uniform backbones.ACS Chem Biol,2011,6:590-599
18 Palermo EF,Sovadinova I,Kuroda K.Structural determinants of antimicrobial activity and biocompatibility in membrane-disrupting methacrylamide random copolymers.Biomacromolecules,2009,10:3098-3107
19 Jiang Y,Yang X,Zhu R,et al.Acid-activated antimicrobial random copolymers:A mechanism-guided design of antimicrobial peptide mimics.Macromolecules,2013,46:3959-3964
20 Xiong M,Lee MW,Mansbach RA,et al.Helical antimicrobial polypeptides with radial amphiphilicity.Proc Natl Acad Sci USA,2015,112:13155-13160
21 Qian Y,Zhang D,Wu Y,et al.The design,synthesis and biological activity study of nylon-3 polymers as mimics of host defense peptides.Acta Polym Sin,2016,1300-1311
22 Liu R,Suárez JM,Weisblum B,et al.Synthetic polymers active against Clostridium difficile vegetative cell growth and spore outgrowth.J Am Chem Soc,2014,136:14498-14504
23 Liu R,Chen X,Hayouka Z,et al.Nylon-3 polymers with selective antifungal activity.J Am Chem Soc,2013,135:5270-5273
24 Liu R,Chen X,Falk SP,et al.Nylon-3 polymers active against drug-resistant Candida albicans biofilms.J Am Chem Soc,2015,137:2183-2186
25 Liu R,Chen X,Chakraborty S,et al.Tuning the biological activity profile of antibacterial polymers via subunit substitution pattern.JAm Chem Soc,2014,136:4410-4418
26 Tew GN,Scott RW,Klein ML,et al.De novo design of antimicrobial polymers,foldamers,and small molecules:From discovery to practical applications.Acc Chem Res,2010,43:30-39
27 Li P,Zhou C,Rayatpisheh S,et al.Cationic peptidopolysaccharides show excellent broad-spectrum antimicrobial activities and high selectivity.Adv Mater,2012,24:4130-4137
28 Niu Y,Padhee S,Wu H,et al.Identification ofγ-AApeptides with potent and broad-spectrum antimicrobial activity.Chem Commun,2011,47:12197
29 Niu Y,Padhee S,Wu H,et al.Lipo-γ-AApeptides as a new class of potent and broad-spectrum antimicrobial agents.J Med Chem,2012,55:4003-4009
30 Padhee S,Hu Y,Niu Y,et al.Non-hemolyticα-AApeptides as antimicrobial peptidomimetics.Chem Commun,2011,47:9729
31 Yarlagadda V,Akkapeddi P,Manjunath GB,et al.Membrane active vancomycin analogues:A strategy to combat bacterial resistance.J Med Chem,2014,57:4558-4568
32 Yarlagadda V,Samaddar S,Paramanandham K,et al.Membrane disruption and enhanced inhibition of cell-wall biosynthesis:Asynergistic approach to tackle vancomycin-resistant bacteria.Angew Chem Int Ed,2015,54:13644-13649
33 Choi H,Chakraborty S,Liu R,et al.Single-cell,time-resolved antimicrobial effects of a highly cationic,random nylon-3 copolymer on live Escherichia coli.ACS Chem Biol,2016,11:113-120
34 Ding X,Duan S,Ding X,et al.Versatile antibacterial materials:An emerging arsenal for combatting bacterial pathogens.Adv Funct Mater,2018,362:1802140
35 Su Y,Tian L,Yu M,et al.Cationic peptidopolysaccharides synthesized by‘click’chemistry with enhanced broad-spectrum antimicrobial activities.Polym Chem,2017,8:3788-3800
36 Pranantyo D,Xu LQ,Hou Z,et al.Increasing bacterial affinity and cytocompatibility with four-arm star glycopolymers and antimicrobialα-polylysine.Polym Chem,2017,8:3364-3373
37 Lu H,Wang J,Lin Y,et al.One-pot synthesis of brush-like polymers via integrated ring-opening metathesis polymerization and polymerization of amino acid N-carboxyanhydrides.J Am Chem Soc,2009,131:13582-13583
38 Wang J,Lu H,Ren Y,et al.Interrupted helical structure of grafted polypeptides in brush-like macromolecules.Macromolecules,2015,44:8699-8708
39 Meereboer NL,Terzi?I,Saidi S,et al.Two-dimensional controlled syntheses of polypeptide molecular brushes via N-carboxyanhydride ring-opening polymerization and ring-opening metathesis polymerization.ACS Macro Lett,2017,6:1031-1035
40 Beers KL,Gaynor SG,Matyjaszewski K,et al.The synthesis of densely grafted copolymers by atom transfer radical polymerization.Macromolecules,1998,31:9413-9415
41 Cheng G,B?ker A,Zhang M,et al.Amphiphilic cylindrical core-shell brushes via a“grafting from”process using atrp.Macromolecules,2001,34:6883-6888
42 Gerle M,Fischer K,Roos S,et al.Main chain conformation and anomalous elution behavior of cylindrical brushes as revealed by GPC/MALLS,light scattering,and SFM.Macromolecules,1999,32:2629-2637
43 Li Z,Ma J,Cheng C,et al.Synthesis of hetero-grafted amphiphilic diblock molecular brushes and their self-assembly in aqueous medium.Macromolecules,2010,43:1182-1184
44 Müllner M,Dodds SJ,Nguyen TH,et al.Size and rigidity of cylindrical polymer brushes dictate long circulating properties in vivo.ACS Nano,2015,9:1294-1304
45 Neugebauer D,Sumerlin BS,Matyjaszewski K,et al.How dense are cylindrical brushes grafted from a multifunctional macroinitiator?Polymer,2004,45:8173-8179
46 Runge MB,Bowden NB.Synthesis of high molecular weight comb block copolymers and their assembly into ordered morphologies in the solid state.J Am Chem Soc,2007,129:10551-10560
47 Xia Y,Kornfield JA,Grubbs RH.Efficient synthesis of narrowly dispersed brush polymers via living ring-opening metathesis polymerization of macromonomers.Macromolecules,2009,42:3761-3766
48 Zheng G,Pan C.Reversible addition-fragmentation transfer polymerization in nanosized micelles formed in situ.Macromolecules,2006,39:95-102
49 Xia Y,Olsen BD,Kornfield JA,et al.Efficient synthesis of narrowly dispersed brush copolymers and study of their assemblies:The importance of side chain arrangement.J Am Chem Soc,2009,131:18525-18532
50 Zhang Y,Yin Q,Lu H,et al.Peg-polypeptide dual brush block copolymers:Synthesis and application in nanoparticle surface pegylation.ACS Macro Lett,2013,2:809-813
51 Gao Q,Yu M,Su Y,et al.Rationally designed dual functional block copolymers for bottlebrush-like coatings:In vitro and in vivo antimicrobial,antibiofilm,and antifouling properties.Acta Biomater,2017,51:112-124
52 Verduzco R,Li X,Pesek SL,et al.Structure,function,self-assembly,and applications of bottlebrush copolymers.Chem Soc Rev,2015,44:2405-2420
53 Lu X,Tran TH,Jia F,et al.Providing oligonucleotides with steric selectivity by brush-polymer-assisted compaction.J Am Chem Soc,2015,137:12466-12469
54 Gao AX,Liao L,Johnson JA.Synthesis of acid-labile peg and pegdoxorubicin-conjugate nanoparticles via brush-first romp.ACSMacro Lett,2014,3:854-857
55 Gao H,Matyjaszewski K.Synthesis of molecular brushes by“grafting onto”method:combination of ATRP and click reactions.J Am Chem Soc,2007,129:6633-6639
56 Guo J,Hong H,Chen G,et al.Theranostic unimolecular micelles based on brush-shaped amphiphilic block copolymers for tumortargeted drug delivery and positron emission tomography imaging.ACS Appl Mater Interfaces,2014,6:21769-21779
57 H?rtz C,Birke A,Kaps L,et al.Cylindrical brush polymers with polysarcosine side chains:A novel biocompatible carrier for biomedical applications.Macromolecules,2015,48:2074-2086
58 Jin X,Sun P,Tong G,et al.Star polymer-based unimolecular micelles and their application in bio-imaging and diagnosis.Biomaterials,2018,178:738-750
59 Li H,Liu H,Nie T,et al.Molecular bottlebrush as a unimolecular vehicle with tunable shape for photothermal cancer therapy.Biomaterials,2018,178:620-629
60 Liao L,Liu J,Dreaden EC,et al.A convergent synthetic platform for single-nanoparticle combination cancer therapy:Ratiometric loading and controlled release of cisplatin,doxorubicin,and camptothecin.J Am Chem Soc,2014,136:5896-5899
61 Müllner M,Mehta D,Nowell CJ,et al.Passive tumour targeting and extravasation of cylindrical polymer brushes in mouse xenografts.Chem Commun,2016,52:9121-9124
62 Sowers MA,McCombs JR,Wang Y,et al.Redox-responsive branched-bottlebrush polymers for in vivo MRI and fluorescence imaging.Nat Commun,2014,5:5460
63 von Erlach T,Zwicker S,Pidhatika B,et al.Formation and characterization of DNA-polymer-condensates based on poly(2-methyl-2-oxazoline)grafted poly(l-lysine)for non-viral delivery of therapeutic DNA.Biomaterials,2011,32:5291-5303
64 Zeng X,Wang L,Liu D,et al.Poly(l-lysine)-based cylindrical copolypeptide brushes as potential drug and gene carriers.Colloid Polym Sci,2016,294:1909-1920
65 Liu R,Masters KS,Gellman SH.Polymer chain length effects on fibroblast attachment on nylon-3-modified surfaces.Biomacromolecules,2012,13:1100-1105
66 Liu R,Chen X,Gellman SH,et al.Nylon-3 polymers that enable selective culture of endothelial cells.J Am Chem Soc,2013,135:16296-16299
67 Liu R,Chen X,Falk SP,et al.Structure-activity relationships among antifungal nylon-3 polymers:identification of materials active against drug-resistant strains of Candida albicans.J Am Chem Soc,2014,136:4333-4342
68 Hou Y,Wang Y,Wang R,et al.Harnessing phosphato-platinum bonding induced supramolecular assembly for systemic cisplatin delivery.ACS Appl Mater Interfaces,2017,9:17757-17768
69 Qian Y,Qi F,Chen Q,et al.Surface modified with a host defense peptide-mimickingΒ-peptide polymer kills bacteria on contact with high efficacy.ACS Appl Mater Interfaces,2018,10:15395-15400
70 Chakraborty S,Liu R,Hayouka Z,et al.Ternary nylon-3 copolymers as host-defense peptide mimics:Beyond hydrophobic and cationic subunits.J Am Chem Soc,2014,136:14530-14535
71 Zhang D,Zhang S,Ma P,et al.Synthetic peptidyl polymer displaying potent activity against gram positive bacteria.J Funct Polym,2018,DOI:10.14133/j.cnki.1008-9357.20180410001
72 Hovakeemian SG,Liu R,Gellman SH,et al.Correlating antimicrobial activity and model membrane leakage induced by nylon-3 polymers and detergents.Soft Matter,2015,11:6840-6851