Oligo(para-phenylenes)s-Oligoarginine Conjugates as Effective Antibacterial Agents with High Plasma Stability and Low Hemolysis

被引：2

作者：

Yuan, Xingyi ^{[1
,2
]}

Wang, Chenhong ^{[2
]}

Chen, Junyi ^{[2
]}

Shu, Xiaoyan ^{[1
]}

Chai, Yao ^{[2
]}

Meng, Zhao ^{[2
]}

Hou, Dabin ^{[1
]}

Li, Chunju ^{[1
,3
]}

Meng, Qingbin ^{[2
]}

机构：

[1] Southwest Univ Sci & Technol, Sch Life Sci & Engn, Mianyang 621010, Sichuan, Peoples R China

[2] Beijing Inst Pharmacol & Toxicol, State Key Lab Toxicol & Med Countermeasures, Beijing 100850, Peoples R China

[3] Tianjin Normal Univ, Coll Chem,Minist Educ, Key Lab Inorgan Organ Hybrid Funct Mat Chem, Tianjin Key Lab Struct & Performance Funct Mol, Tianjin 300387, Peoples R China

来源：

ACS APPLIED BIO MATERIALS | 2020年 / 3卷 / 12期

基金：

中国国家自然科学基金;

关键词：

antibacterial agents; oligo(para-phenylenes)s-oligoarginine conjugates; plasma stability; biocompatibility; low cytotoxicity; DE-NOVO DESIGN; ANTIMICROBIAL PEPTIDES; BLOCK-COPOLYMERS; MIMICS; LYSINE; PLATFORM; BROAD;

D O I：

10.1021/acsabm.0c00904

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

Bacterial infections have become a global threat to human health, and the design of antibacterial agents is always an urgent task for biomedicine. Amphiphilic antibacterial agents with a different mechanism of action from traditional antibiotics have attracted researchers' attention more and more in recent years. In this work, a series of antibacterial conjugates composed of oligo(para-phenylenes)s and oligoarginine were synthesized, and their antibacterial activity was investigated. 2,2'-Biphenyl, 2,2 ''-terphenyl, and 2,2'''-quaterphenyl were conjugated with one or two triarginines by "click" chemical reactions to form compounds. The conjugates showed antibacterial activity against the typical Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria, relatively low cytotoxicity to L929 cell line, and hemolytic activity in a certain range of concentration. Among these conjugates, 2,2'''-quaterphenyl-triarginine conjugate (2,2'''-QP-1) showed the highest antibacterial activity against both E. coli and S. aureus. Besides, it presented better stability in plasma compared with the positive control peixiganan. The antimicrobial mechanism of 2,2'''-QP-1 was also investigated by transmission electron microscopy and confocal laser scanning microscopy, showing that 2,2'''-QP-1 could interact with the bacterial membrane and then disrupt the membrane structure. This work demonstrated a prospective approach for the design of antibacterial agents with highly effective antibacterial activity, high stability in plasma, and low cytotoxicity.

引用

页码：8532 / 8541

页数：10