Peptidyl Vinyl Ketone Irreversible Inhibitors of Rhodesain: Modifications of the P2 Fragment.,ChemMedChem

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Peptidyl Vinyl Ketone Irreversible Inhibitors of Rhodesain: Modifications of the P2 Fragment.
ChemMedChem ( IF 3.6 ) Pub Date : 2020-06-21 , DOI: 10.1002/cmdc.202000360
Santina Maiorana ₁ , Roberta Ettari ₁ , Santo Previti ₁ , Giorgio Amendola ₂ , Annika Wagner _{3,

4} , Sandro Cosconati ₂ , Ute A Hellmich _{3,

4} , Tanja Schirmeister ₅ , Maria Zappalà ₁

Affiliation

In this paper, we report the design, synthesis and biological investigation of a series of peptidyl vinyl ketones obtained by modifying the P2 fragment of previously reported highly potent inhibitors of rhodesain, the main cysteine protease of Trypanosoma brucei rhodesiense. Investigation of the structure–activity relationship led us to identify new rhodesain inhibitors endowed with an improved selectivity profile (a selectivity index of up to 22 000 towards the target enzyme), and/or an improved antitrypanosomal activity in the sub‐micromolar range.

中文翻译：

Rhodesain的肽基乙烯基酮不可逆抑制剂：P2片段的修饰。

在本文中，我们报告了一系列肽基乙烯基酮的设计，合成和生物学研究，这些肽基肽是通过修饰先前报道的强效罗氏菌素（罗氏锥虫的主要半胱氨酸蛋白酶）的P2片段而获得的。通过对结构-活性关系的研究，我们发现了新的罗丹蛋白酶抑制剂，这些抑制剂具有改进的选择性特征（对目标酶的选择性指数高达22 000）和/或在亚微摩尔范围内的抗锥虫活性提高。

更新日期：2020-08-21

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