Structure-based design and synthesis of highly potent SARS-CoV 3CL protease inhibitors

Yi Ming Shao; Wen Bin Yang; Hung Pin Peng; Min Feng Hsu; Keng Chang Tsai; Tun Hsun Kuo; Andrew H.J. Wang; Po Huang Liang; Chun Hung Lin; An Suei Yang; Chi Huey Wong

doi:10.1002/cbic.200700254

Structure-based design and synthesis of highly potent SARS-CoV 3CL protease inhibitors

Yi Ming Shao, Wen Bin Yang, Hung Pin Peng, Min Feng Hsu, Keng Chang Tsai, Tun Hsun Kuo, Andrew H.J. Wang, Po Huang Liang, Chun Hung Lin, An Suei Yang, Chi Huey Wong

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

33 Citations (Scopus)

Abstract

In a successful example of lead optimization by computer modeling prediction, computational technology was used to optimize a lead inhibitor (TL-3) of the SARS-CoV 3CL protease. A novel C₂-symmetric diol (1) was then designed and synthesized, and displayed higher affinity than the original lead compound by one order of magnitude in its inhibition constant (0.6→0.073 μM). We believe that this approach has provided a platform for further lead optimization. (Chemical Equation Presented).

Original language	English
Pages (from-to)	1654-1657
Number of pages	4
Journal	ChemBioChem
Volume	8
Issue number	14
DOIs	https://doi.org/10.1002/cbic.200700254
Publication status	Published - Sept 24 2007
Externally published	Yes

Keywords

Computer modeling
Inhibitors
Medicinal chemistry
Proteases
Structure-based design

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Organic Chemistry

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10.1002/cbic.200700254

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AU - Shao, Yi Ming

AU - Yang, Wen Bin

AU - Peng, Hung Pin

AU - Hsu, Min Feng

AU - Tsai, Keng Chang

AU - Kuo, Tun Hsun

AU - Wang, Andrew H.J.

AU - Liang, Po Huang

AU - Lin, Chun Hung

AU - Yang, An Suei

AU - Wong, Chi Huey

PY - 2007/9/24

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KW - Medicinal chemistry

KW - Proteases

KW - Structure-based design

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Structure-based design and synthesis of highly potent SARS-CoV 3CL protease inhibitors

Abstract

Keywords

ASJC Scopus subject areas

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