Structure-based design, synthesis, and biological evaluation of peptidomimetic SARS-CoV 3CLpro inhibitors

Arun K. Ghosh; Kai Xi; Valerie Grum-Tokars; Xiaoming Xu; Kiira Ratia; Wentao Fu; Katherine V. Houser; Susan C. Baker; Michael E. Johnson; Andrew D. Mesecar

doi:10.1016/j.bmcl.2007.08.031

Structure-based design, synthesis, and biological evaluation of peptidomimetic SARS-CoV 3CLpro inhibitors

Arun K. Ghosh^*, Kai Xi, Valerie Grum-Tokars, Xiaoming Xu, Kiira Ratia, Wentao Fu, Katherine V. Houser, Susan C. Baker, Michael E. Johnson, Andrew D. Mesecar

^*Corresponding author for this work

Pharmacology

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

89 Scopus citations

Abstract

Structure-based design, synthesis, and biological evaluation of a series of peptidomimetic severe acute respiratory syndrome-coronavirus chymotrypsin-like protease inhibitors are described. These inhibitors were designed and synthesized based upon our X-ray crystal structure of inhibitor 1 bound to SARS-CoV 3CLpro. Incorporation of Boc-Ser as the P₄-ligand resulted in enhanced SARS-CoV 3CLpro inhibitory activity. Structural analysis of the inhibitor-bound X-ray structure revealed high binding affinity toward the enzyme.

Original language	English (US)
Pages (from-to)	5876-5880
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	21
DOIs	https://doi.org/10.1016/j.bmcl.2007.08.031
State	Published - Nov 1 2007

Keywords

Design
Inhibitor
SARS 3CLpro
Synthesis
X-ray structure

ASJC Scopus subject areas

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

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10.1016/j.bmcl.2007.08.031

Cite this

@article{f73b7e6092a5436bb7f51a788982a560,

title = "Structure-based design, synthesis, and biological evaluation of peptidomimetic SARS-CoV 3CLpro inhibitors",

abstract = "Structure-based design, synthesis, and biological evaluation of a series of peptidomimetic severe acute respiratory syndrome-coronavirus chymotrypsin-like protease inhibitors are described. These inhibitors were designed and synthesized based upon our X-ray crystal structure of inhibitor 1 bound to SARS-CoV 3CLpro. Incorporation of Boc-Ser as the P4-ligand resulted in enhanced SARS-CoV 3CLpro inhibitory activity. Structural analysis of the inhibitor-bound X-ray structure revealed high binding affinity toward the enzyme.",

keywords = "Design, Inhibitor, SARS 3CLpro, Synthesis, X-ray structure",

author = "Ghosh, {Arun K.} and Kai Xi and Valerie Grum-Tokars and Xiaoming Xu and Kiira Ratia and Wentao Fu and Houser, {Katherine V.} and Baker, {Susan C.} and Johnson, {Michael E.} and Mesecar, {Andrew D.}",

note = "Funding Information: The financial support of this work is provided by the National Institute of Health (NIAID, P01 A1060915). ",

year = "2007",

month = nov,

day = "1",

doi = "10.1016/j.bmcl.2007.08.031",

language = "English (US)",

volume = "17",

pages = "5876--5880",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd",

number = "21",

}

TY - JOUR

T1 - Structure-based design, synthesis, and biological evaluation of peptidomimetic SARS-CoV 3CLpro inhibitors

AU - Ghosh, Arun K.

AU - Xi, Kai

AU - Grum-Tokars, Valerie

AU - Xu, Xiaoming

AU - Ratia, Kiira

AU - Fu, Wentao

AU - Houser, Katherine V.

AU - Baker, Susan C.

AU - Johnson, Michael E.

AU - Mesecar, Andrew D.

N1 - Funding Information: The financial support of this work is provided by the National Institute of Health (NIAID, P01 A1060915).

PY - 2007/11/1

Y1 - 2007/11/1

N2 - Structure-based design, synthesis, and biological evaluation of a series of peptidomimetic severe acute respiratory syndrome-coronavirus chymotrypsin-like protease inhibitors are described. These inhibitors were designed and synthesized based upon our X-ray crystal structure of inhibitor 1 bound to SARS-CoV 3CLpro. Incorporation of Boc-Ser as the P4-ligand resulted in enhanced SARS-CoV 3CLpro inhibitory activity. Structural analysis of the inhibitor-bound X-ray structure revealed high binding affinity toward the enzyme.

AB - Structure-based design, synthesis, and biological evaluation of a series of peptidomimetic severe acute respiratory syndrome-coronavirus chymotrypsin-like protease inhibitors are described. These inhibitors were designed and synthesized based upon our X-ray crystal structure of inhibitor 1 bound to SARS-CoV 3CLpro. Incorporation of Boc-Ser as the P4-ligand resulted in enhanced SARS-CoV 3CLpro inhibitory activity. Structural analysis of the inhibitor-bound X-ray structure revealed high binding affinity toward the enzyme.

KW - Design

KW - Inhibitor

KW - SARS 3CLpro

KW - Synthesis

KW - X-ray structure

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DO - 10.1016/j.bmcl.2007.08.031

M3 - Article

C2 - 17855091

AN - SCOPUS:34548830820

SN - 0960-894X

VL - 17

SP - 5876

EP - 5880

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 21

ER -

Structure-based design, synthesis, and biological evaluation of peptidomimetic SARS-CoV 3CLpro inhibitors

Abstract

Keywords

ASJC Scopus subject areas

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