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通过筛选组合肽库鉴定克氏锥虫80 kDa蛋白酶的抑制剂。

Identification of inhibitors of an 80 kDa protease from Trypanosoma cruzi through the screening of a combinatorial peptide library.

作者信息

Vendeville S, Buisine E, Williard X, Schrevel J, Grellier P, Santana J, Sergheraert C

机构信息

Institut de Biologie de Lille-Institut Pasteur de Lille, URA CNRS 1309, Faculté de Pharmacie, Université de Lille II, France.

出版信息

Chem Pharm Bull (Tokyo). 1999 Feb;47(2):194-8. doi: 10.1248/cpb.47.194.

DOI:10.1248/cpb.47.194
PMID:10071854
Abstract

Two orthogonal peptide combinatorial libraries were screened to discover inhibitors of Tc80 protease, a novel target from Trypanosoma cruzi involved in host cell invasion. These libraries were composed of 15,625 structurally diversified tripeptides, partitioned in 125 mixtures. The screening led to a low micromolar inhibitor which was actually an HF cleavage by-product H-Ipe-D-Tic-D-Glu(S-paratolyl)-OH. IC50 values of several analogous molecules of this hit were determined and are discussed. For the best compounds, conformational analysis revealed a high degree of similarity in shape with a potent prolylendopeptidase inhibitor, SUAM-1221.

摘要

筛选了两个正交肽组合文库，以发现克氏锥虫中一种参与宿主细胞入侵的新型靶点Tc80蛋白酶的抑制剂。这些文库由15625种结构多样的三肽组成，分为125个混合物。筛选得到了一种低微摩尔浓度的抑制剂，它实际上是一种HF裂解副产物H-Ipe-D-Tic-D-Glu（对甲苯基）-OH。测定并讨论了该命中物几种类似分子的IC50值。对于最佳化合物，构象分析显示其形状与一种有效的脯氨酰内肽酶抑制剂SUAM-1221高度相似。

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