Discovery of covalent enzyme inhibitors using virtual docking of covalent fragments

Sandipan Roy Chowdhury; Steven Kennedy; Kai Zhu; Rama Mishra; Patrick Chuong; Alyssa uyen Nguyen; Stefan G. Kathman; Alexander V. Statsyuk

doi:10.1016/j.bmcl.2018.11.019

Discovery of covalent enzyme inhibitors using virtual docking of covalent fragments

Sandipan Roy Chowdhury, Steven Kennedy, Kai Zhu, Rama Mishra, Patrick Chuong, Alyssa uyen Nguyen, Stefan G. Kathman, Alexander V. Statsyuk^*

^*Corresponding author for this work

Biochemistry and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

Here we present a virtual docking screen of 1648 commercially available covalent fragments, and identified covalent inhibitors of cysteine protease cathepsin L. These inhibitors did not inhibit closely related protease cathepsin B. Thus, we have established virtual docking of covalent fragments as an approach to discover covalent enzyme inhibitors.

Original language	English (US)
Pages (from-to)	36-39
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	29
Issue number	1
DOIs	https://doi.org/10.1016/j.bmcl.2018.11.019
State	Published - Jan 1 2019

Funding

This work was supported in part by National Institutes of Health Awards R01GM115632 (to A.V.S.) and T32GM105538 (to S.G.K.), William & Ella Owens Research Foundation, and the University of Houston. A.V.S. is a Pew Scholar in the Biomedical Sciences, supported by the Pew Charitable Trusts . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health . The authors declare that they have no conflicts of interest with the contents of this article.

ASJC Scopus subject areas

Drug Discovery
Molecular Medicine
Molecular Biology
Biochemistry
Clinical Biochemistry
Pharmaceutical Science
Organic Chemistry

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abstract = "Here we present a virtual docking screen of 1648 commercially available covalent fragments, and identified covalent inhibitors of cysteine protease cathepsin L. These inhibitors did not inhibit closely related protease cathepsin B. Thus, we have established virtual docking of covalent fragments as an approach to discover covalent enzyme inhibitors.",

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AU - Kennedy, Steven

AU - Zhu, Kai

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AU - Chuong, Patrick

AU - Nguyen, Alyssa uyen

AU - Kathman, Stefan G.

AU - Statsyuk, Alexander V.

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Discovery of covalent enzyme inhibitors using virtual docking of covalent fragments

Abstract

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