细胞毒性
化学
抗菌剂
抗菌肽
肽
溶解
生物化学
两亲性
细胞
膜透性
流式细胞术
膜
体外
分子生物学
生物
有机化学
聚合物
共聚物
作者
Zhi Mao,Jing Yang,Jun Han,Ling Gao,Hongxia Liu,Zhaoxin Lu,Haizhen Zhao,Xiaomei Bie
标识
DOI:10.1021/acs.jmedchem.6b00922
摘要
Antimicrobial peptides (AMPs) have gained increasing attention, as they can overcome recurring microbial invasions. However, their poor antimicrobial activity and potential cytotoxicity remain impediments to their clinical applications as novel therapeutic agents. To enhance the antimicrobial activity and cell selectivity of AMPs, a series of amphiphilic peptides based on leucocin A were designed by substituting noncharged hydrophilic residues with arginine and leucine. Of the engineered peptides, peptide 7 (WRL3) (WLRAFRRLVRRLARGLRR-NH2) exhibited the highest cell selectivity toward bacterial cells over erythrocytes and macrophages. Fluorescent measurements and microscopic observations demonstrated that 7 increased cell membrane permeability and disrupted membrane envelope integrity, and eventually led to whole cell lysis. Additionally, flow cytometry analysis and subcellular localization studies revealed that 7 showed potent cytotoxicity against human hepatoma cells HepG2. In summary, the data indicate that these engineered peptides, in particular 7, have enormous promise for antibacterial and/or antitumor therapeutics.
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