Revolutionizing Antimicrobial Biomaterials:Integrating an Enzyme Degradation‑Resistant Sequence into Self‑Assembled Nanosystems to Overcome Stability Limitations of Peptide‑Based Drugs  

作　　者：Weikang Yu Xu Guo Qingrui Li Xuefeng Li Yingxin Wei Changxuan Shao Licong Zhang Jiajun Wang Anshan Shan 

机构地区：[1]College of Animal Science and Technology,Northeast Agricultural University,Harbin 150030,People’s Republic of China

出　　处：《Advanced Fiber Materials》2024年第4期1188-1211,共24页先进纤维材料（英文）

基　　金：supported by the National Natural Science Foundation of China(Nos.32030101,32272914,and 32002215);the Heilongjiang Provincial Collaborative Innovation Achievement Project for Universities—Incubation Project(LJGXCG2022-022);the Heilongjiang Touyan Innovation Team Program(No.54600112);the Natural Science Foundation of Heilongjiang Province(YQ2022C015).

摘　　要：Incorporating enzyme-resistant peptide sequences into self-assembled nanosystems is a promising strategy to enhance the stability and versatility of peptide-based antibacterial drugs,aiming to replace ineffective antibiotics.By combining newly designed enzymatic-resistant sequences with synthetically derived compounds bearing single,double,triple,or quadruple aromatic rings.A series of nanoscale antimicrobial self-assembled short peptides for the purpose of combating bacterial infections are generated.Nap^(*)(Nap–DNal–Nal–Dab–Dab–NH2,where Nap represents the 1-naphthylacetyl group)possesses the greatest clinical potential(GMSI=23.96)among the peptides in this series.At high concentrations in an aqueous environment,Nap^(*)spontaneously generates nanofibers to capture bacteria and prevent their evasion,exhibiting broad-spectrum antimicrobial effects and exceptional biocompatibility.In the presence of physiological salt ions and serum,the antimicrobial agent exhibits strong effectiveness and retains impressive resistance even when exposed to high levels of proteases(trypsin,chymotrypsin,pepsin).Nap^(*)exhibits negligible in vivo toxicity and effectively alleviates systemic bacterial infections in mice.Mechanistically,Nap^(*)initially captures bacteria and induces bacterial cell death primarily through membrane dissolution,achieved by multiple synergistic mechanisms.In summary,these advances have the potential to greatly expedite the clinical evolution of nanomaterials based on short peptides combined with naphthyl groups and foster the development of peptides integrated with self-assembled systems in this domain.

关 键 词：NAPHTHYL NANOFIBERS Antimicrobial peptide Self-assembled Protease resistance Antibacterial mechanism 

分 类 号：R318.08[医药卫生—生物医学工程]