Cell penetration of oxadiazole-containing macrocycles†

IF 4.2 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY RSC Chemical Biology Pub Date : 2024-01-15 DOI:10.1039/D3CB00201B
Sungjoon Huh, Nefeli Batistatou, Jing Wang, George J. Saunders, Joshua A. Kritzer and Andrei K. Yudin
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Abstract

Passive membrane permeability is an important property in drug discovery and biological probe design. To elucidate the cell-penetrating ability of oxadiazole-containing (Odz) peptides, we employed the Chloroalkane Penetration Assay. The present study demonstrates that Odz cyclic peptides can be highly cell-penetrant depending on the position of specific side chains and the chloroalkane tag. Solution NMR shows that Odz cyclic peptides adopt a β-turn conformation. However, despite observing high cell penetration, we observed low passive permeability in experiments with artificial membranes. These findings highlight the complexity of controlling cell penetration for conformationally sensitive macrocycles and suggest that Odz cyclic peptides may provide a framework for designing cell-penetrant cyclic peptides.

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含噁二唑的大环的细胞渗透性
被动膜渗透性是药物发现和生物探针设计中的一项重要特性。为了阐明含噁二唑(Odz)多肽的细胞穿透能力,我们采用了氯代烃穿透试验。本研究表明,根据特定侧链和氯代烃标签的位置,Odz 环肽具有很强的细胞穿透性。溶液核磁共振显示,Odz 环肽呈 β 转构象。然而,尽管观察到了高细胞渗透性,我们还是在人工膜实验中观察到了低被动渗透性。这些发现突显了控制构象敏感大环的细胞渗透性的复杂性,并表明 Odz 环肽可能为设计细胞渗透性环肽提供了一个框架。
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来源期刊
CiteScore
6.10
自引率
0.00%
发文量
128
审稿时长
10 weeks
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