Targeting Intracellular Pathogenic Bacteria Through N-Terminal Modification of Cationic Amphiphilic Polyproline Helices

被引:9
|
作者
Dietsche, Thomas A. [1 ]
Eldesouky, Hassan E. [2 ]
Zeiders, Samantha M. [1 ]
Seleem, Mohamed N. [2 ]
Chmielewski, Jean [1 ]
机构
[1] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA
[2] Purdue Univ, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA
来源
JOURNAL OF ORGANIC CHEMISTRY | 2020年 / 85卷 / 11期
基金
美国国家科学基金会;
关键词
ACINETOBACTER-BAUMANNII; NANOPARTICLES; PEPTIDES;
D O I
10.1021/acs.joc.0c00871
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Intracellular pathogens can thrive within mammalian cells and are inaccessible to many antimicrobial agents. Herein, we present a facile method of enhancing the cell penetrating and antibacterial properties of cationic amphiphilic polyproline helices (CAPHs) with modifications to the hydrophobic moiety at the N-terminus. These altered CAPHs display superior cell penetration within macrophage cells, and in some cases, minimal cytotoxicity. Furthermore, one CAPH, Pentyl-P14 exhibited excellent antibacterial activity against multiple strains of pathogenic bacteria and promoted the clearance of intracellular Shigella within macrophages.
引用
收藏
页码:7468 / 7475
页数:8
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