Predicting the Reactivity of Nitrile-Carrying Compounds with Cysteine: A Combined Computational and Experimental Study

被引：82

作者：

Berteotti, Anna ^{[1
]}

Vacondio, Federica ^{[2
]}

Lodola, Alessio ^{[2
]}

Bassi, Michele ^{[2
]}

Silva, Claudia ^{[2
]}

Mor, Marco ^{[2
]}

Cavalli, Andrea ^{[1
,3
]}

机构：

[1] Italian Inst Technol, I-16163 Genoa, Italy

[2] Univ Parma, Dipartimento Farm, I-43124 Parma, Italy

[3] Univ Bologna, Dept Pharm & Biotechnol, I-40126 Bologna, Italy

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2014年 / 5卷 / 05期

关键词：

Cysteine; nucleophilic attack; DFT; nitrile reactivity; CATHEPSIN-K; CATALYTIC MECHANISM; INHIBITORS; PROTEASE; DISCOVERY;

D O I：

10.1021/ml400489b

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Here, we report on a mechanistic investigation based on DFT calculations and kinetic measures aimed at determining the energetics related to the cysteine nucleophilic attack on nitrile-carrying compounds. Activation energies were found to correlate well with experimental kinetic measures of reactivity with cysteine in phosphate buffer. The agreement between computations and experiments points to this DFT-based approach as a tool for predicting both nitrile reactivity toward cysteines and the toxicity of nitriles as electrophile agents.

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页码：501 / 505

页数：5

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