Design and Synthesis of Peptidomimetic Severe Acute Respiratory Syndrome Chymotrypsin-like Protease Inhibitors
Identifieur interne : 000346 ( Istex/Curation ); précédent : 000345; suivant : 000347Design and Synthesis of Peptidomimetic Severe Acute Respiratory Syndrome Chymotrypsin-like Protease Inhibitors
Auteurs : Arun K. Ghosh [Géorgie (pays), États-Unis] ; Kai Xi [Géorgie (pays), États-Unis] ; Kiira Ratia [Géorgie (pays)] ; Bernard D. Santarsiero [Géorgie (pays)] ; Wentao Fu [Géorgie (pays)] ; Brian H. Harcourt [Géorgie (pays)] ; Paul A. Rota [Géorgie (pays)] ; Susan C. Baker [Géorgie (pays)] ; Michael E. Johnson [Géorgie (pays)] ; Andrew D. Mesecar [Géorgie (pays)]Source :
- Journal of Medicinal Chemistry [ 0022-2623 ] ; 2005.
Abstract
Design, synthesis, and biological evaluation of peptidomimetic severe acute respiratory syndrome chymotrypsin-like protease (SARS-3CLpro) inhibitors for severe acute respiratory syndrome coronavirus (SARS-CoV) are described. These inhibitors exhibited antiviral activity against SARS-CoV in infected cells in the micromolar range. An X-ray crystal structure of our lead inhibitor (4) bound to SARS-3CLpro provided important drug-design templates for the design of small-molecule inhibitors.
Url:
DOI: 10.1021/jm050548m
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<sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Design and Synthesis of Peptidomimetic
Severe Acute Respiratory Syndrome
Chymotrypsin-like Protease Inhibitors</title>
<author><name sortKey="Ghosh, Arun K" sort="Ghosh, Arun K" uniqKey="Ghosh A" first="Arun K." last="Ghosh">Arun K. Ghosh</name>
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<wicri:regionArea>Departments of Chemistry and Medicinal Chemistry,Purdue University, West Lafayette, Indiana 47907,Department of Chemistry, University of Illinois at Chicago,Chicago, Illinois 60607, Center for PharmaceuticalBiotechnology and Department of Medicinal Chemistry andPharmacognosy, University of Illinois at Chicago, 900 S.Ashland, Illinois 60607, Department of Microbiology andImmunology, Loyola University of Chicago, Stritch School ofMedicine, Maywood, Illinois, and Center for Disease Controland Prevention, Atlanta</wicri:regionArea>
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<affiliation><mods:affiliation> Purdue University.</mods:affiliation>
</affiliation>
<affiliation wicri:level="4"><mods:affiliation> Department of Chemistry, University of Illinois at Chicago.</mods:affiliation>
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</placeName>
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<affiliation wicri:level="1"><mods:affiliation> To whom correspondence should be addressed. Phone: 765-494-5323. Fax: 765-496-1612. E-mail: akghosh@purdue.edu.</mods:affiliation>
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<affiliation><mods:affiliation> Purdue University.</mods:affiliation>
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<author><name sortKey="Ratia, Kiira" sort="Ratia, Kiira" uniqKey="Ratia K" first="Kiira" last="Ratia">Kiira Ratia</name>
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<author><name sortKey="Fu, Wentao" sort="Fu, Wentao" uniqKey="Fu W" first="Wentao" last="Fu">Wentao Fu</name>
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<author><name sortKey="Harcourt, Brian H" sort="Harcourt, Brian H" uniqKey="Harcourt B" first="Brian H." last="Harcourt">Brian H. Harcourt</name>
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<wicri:regionArea>Departments of Chemistry and Medicinal Chemistry,Purdue University, West Lafayette, Indiana 47907,Department of Chemistry, University of Illinois at Chicago,Chicago, Illinois 60607, Center for PharmaceuticalBiotechnology and Department of Medicinal Chemistry andPharmacognosy, University of Illinois at Chicago, 900 S.Ashland, Illinois 60607, Department of Microbiology andImmunology, Loyola University of Chicago, Stritch School ofMedicine, Maywood, Illinois, and Center for Disease Controland Prevention, Atlanta</wicri:regionArea>
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<affiliation><mods:affiliation> Center for Disease Control and Prevention.</mods:affiliation>
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<country xml:lang="fr">Géorgie (pays)</country>
<wicri:regionArea>Departments of Chemistry and Medicinal Chemistry,Purdue University, West Lafayette, Indiana 47907,Department of Chemistry, University of Illinois at Chicago,Chicago, Illinois 60607, Center for PharmaceuticalBiotechnology and Department of Medicinal Chemistry andPharmacognosy, University of Illinois at Chicago, 900 S.Ashland, Illinois 60607, Department of Microbiology andImmunology, Loyola University of Chicago, Stritch School ofMedicine, Maywood, Illinois, and Center for Disease Controland Prevention, Atlanta</wicri:regionArea>
</affiliation>
<affiliation><mods:affiliation> Center for Disease Control and Prevention.</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Baker, Susan C" sort="Baker, Susan C" uniqKey="Baker S" first="Susan C." last="Baker">Susan C. Baker</name>
<affiliation wicri:level="1"><mods:affiliation>Departments of Chemistry and Medicinal Chemistry,Purdue University, West Lafayette, Indiana 47907,Department of Chemistry, University of Illinois at Chicago,Chicago, Illinois 60607, Center for PharmaceuticalBiotechnology and Department of Medicinal Chemistry andPharmacognosy, University of Illinois at Chicago, 900 S.Ashland, Illinois 60607, Department of Microbiology andImmunology, Loyola University of Chicago, Stritch School ofMedicine, Maywood, Illinois, and Center for Disease Controland Prevention, Atlanta, Georgia</mods:affiliation>
<country xml:lang="fr">Géorgie (pays)</country>
<wicri:regionArea>Departments of Chemistry and Medicinal Chemistry,Purdue University, West Lafayette, Indiana 47907,Department of Chemistry, University of Illinois at Chicago,Chicago, Illinois 60607, Center for PharmaceuticalBiotechnology and Department of Medicinal Chemistry andPharmacognosy, University of Illinois at Chicago, 900 S.Ashland, Illinois 60607, Department of Microbiology andImmunology, Loyola University of Chicago, Stritch School ofMedicine, Maywood, Illinois, and Center for Disease Controland Prevention, Atlanta</wicri:regionArea>
</affiliation>
<affiliation><mods:affiliation> Loyola University of Chicago.</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Johnson, Michael E" sort="Johnson, Michael E" uniqKey="Johnson M" first="Michael E." last="Johnson">Michael E. Johnson</name>
<affiliation wicri:level="1"><mods:affiliation>Departments of Chemistry and Medicinal Chemistry,Purdue University, West Lafayette, Indiana 47907,Department of Chemistry, University of Illinois at Chicago,Chicago, Illinois 60607, Center for PharmaceuticalBiotechnology and Department of Medicinal Chemistry andPharmacognosy, University of Illinois at Chicago, 900 S.Ashland, Illinois 60607, Department of Microbiology andImmunology, Loyola University of Chicago, Stritch School ofMedicine, Maywood, Illinois, and Center for Disease Controland Prevention, Atlanta, Georgia</mods:affiliation>
<country xml:lang="fr">Géorgie (pays)</country>
<wicri:regionArea>Departments of Chemistry and Medicinal Chemistry,Purdue University, West Lafayette, Indiana 47907,Department of Chemistry, University of Illinois at Chicago,Chicago, Illinois 60607, Center for PharmaceuticalBiotechnology and Department of Medicinal Chemistry andPharmacognosy, University of Illinois at Chicago, 900 S.Ashland, Illinois 60607, Department of Microbiology andImmunology, Loyola University of Chicago, Stritch School ofMedicine, Maywood, Illinois, and Center for Disease Controland Prevention, Atlanta</wicri:regionArea>
</affiliation>
<affiliation><mods:affiliation> Center for Pharmaceutical Biotechnology and Department ofMedicinal Chemistry and Pharmacognosy, University of Illinois atChicago.</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Mesecar, Andrew D" sort="Mesecar, Andrew D" uniqKey="Mesecar A" first="Andrew D." last="Mesecar">Andrew D. Mesecar</name>
<affiliation wicri:level="1"><mods:affiliation>Departments of Chemistry and Medicinal Chemistry,Purdue University, West Lafayette, Indiana 47907,Department of Chemistry, University of Illinois at Chicago,Chicago, Illinois 60607, Center for PharmaceuticalBiotechnology and Department of Medicinal Chemistry andPharmacognosy, University of Illinois at Chicago, 900 S.Ashland, Illinois 60607, Department of Microbiology andImmunology, Loyola University of Chicago, Stritch School ofMedicine, Maywood, Illinois, and Center for Disease Controland Prevention, Atlanta, Georgia</mods:affiliation>
<country xml:lang="fr">Géorgie (pays)</country>
<wicri:regionArea>Departments of Chemistry and Medicinal Chemistry,Purdue University, West Lafayette, Indiana 47907,Department of Chemistry, University of Illinois at Chicago,Chicago, Illinois 60607, Center for PharmaceuticalBiotechnology and Department of Medicinal Chemistry andPharmacognosy, University of Illinois at Chicago, 900 S.Ashland, Illinois 60607, Department of Microbiology andImmunology, Loyola University of Chicago, Stritch School ofMedicine, Maywood, Illinois, and Center for Disease Controland Prevention, Atlanta</wicri:regionArea>
</affiliation>
<affiliation><mods:affiliation> Center for Pharmaceutical Biotechnology and Department ofMedicinal Chemistry and Pharmacognosy, University of Illinois atChicago.</mods:affiliation>
</affiliation>
</author>
</analytic>
<monogr></monogr>
<series><title level="j" type="main">Journal of Medicinal Chemistry</title>
<title level="j" type="abbrev">J. Med. Chem.</title>
<idno type="ISSN">0022-2623</idno>
<idno type="eISSN">1520-4804</idno>
<imprint><publisher>American Chemical Society</publisher>
<date type="e-published" when="2005-10-04">2005</date>
<date when="2005-11-03">2005</date>
<biblScope unit="vol">48</biblScope>
<biblScope unit="issue">22</biblScope>
<biblScope unit="page" from="6767">6767</biblScope>
<biblScope unit="page" to="6771">6771</biblScope>
</imprint>
<idno type="ISSN">0022-2623</idno>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><idno type="ISSN">0022-2623</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract">Design, synthesis, and biological evaluation of peptidomimetic severe acute respiratory syndrome chymotrypsin-like protease (SARS-3CLpro) inhibitors for severe acute respiratory syndrome coronavirus (SARS-CoV) are described. These inhibitors exhibited antiviral activity against SARS-CoV in infected cells in the micromolar range. An X-ray crystal structure of our lead inhibitor (4) bound to SARS-3CLpro provided important drug-design templates for the design of small-molecule inhibitors.</div>
</front>
</TEI>
</record>
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