Targeting Intracellular Pathogenic Bacteria Through N-Terminal Modification of Cationic Amphiphilic Polyproline Helices
Targeting Intracellular Pathogenic Bacteria Through N-Terminal Modification of Cationic Amphiphilic Polyproline Helices
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DOI：
10.1021/acs.joc.0c00871
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发表时间：
2020-06-05
影响因子：
3.6
通讯作者：
Chmielewski, Jean
中科院分区：
文献类型：
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作者：
Dietsche, Thomas A.;Eldesouky, Hassan E.;Chmielewski, Jean
细胞内病原体可以在哺乳动物细胞内繁殖，并且许多抗菌剂无法接近。在此，我们提出了一种简便的方法，提高细胞穿透和抗菌性能的阳离子两亲性聚脯氨酸螺旋（CAPH）的N-末端的疏水部分的修改。这些改变的CAPH在巨噬细胞内显示出上级细胞穿透性，并且在某些情况下显示出最小的细胞毒性。此外，一种CAPH，戊基-P14对多种致病菌株表现出优异的抗菌活性，并促进巨噬细胞内志贺氏菌的清除。
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.