针对肽基脯氨酰顺反异构酶Pin1生成一种细胞可渗透的环七肽抑制剂。
Generation of a cell-permeable cycloheptapeptidyl inhibitor against the peptidyl-prolyl isomerase Pin1.
作者信息
Bedewy Walaa, Liao Hui, Abou-Taleb Nageh A, Hammad Sherif F, Nasr Tamer, Pei Dehua
机构信息
Department of Chemistry and Biochemistry, The Ohio State University, 484 West 12th Avenue, Columbus, Ohio 43210, USA.
出版信息
Org Biomol Chem. 2017 May 31;15(21):4540-4543. doi: 10.1039/c7ob00430c.
Abstract
Cyclic peptides are capable of binding and modulating challenging drug targets including protein-protein interactions. However, their lack of membrane permeability prevents their application against intracellular targets. In this study, we show that it is possible to design a cell-permeable and biologically active cycloheptapeptide inhibitor against the intracellular enzyme peptidyl-prolyl isomerase Pin1 by integrating cell-penetrating and target-binding sequences.
摘要
环肽能够结合并调节具有挑战性的药物靶点，包括蛋白质-蛋白质相互作用。然而，它们缺乏膜通透性，这阻碍了它们用于对抗细胞内靶点。在本研究中，我们表明，通过整合细胞穿透序列和靶点结合序列，有可能设计出一种针对细胞内酶肽基脯氨酰异构酶Pin1的细胞可渗透且具有生物活性的环庚肽抑制剂。
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