Structure-based design, synthesis, and biological evaluation of peptidomimetic SARS-CoV 3CLpro inhibitors
Identifieur interne : 000330 ( PascalFrancis/Checkpoint ); précédent : 000329; suivant : 000331Structure-based design, synthesis, and biological evaluation of peptidomimetic SARS-CoV 3CLpro inhibitors
Auteurs : Arun K. Ghosh [États-Unis] ; KAI XI [États-Unis] ; Valerie Grum-Tokars [États-Unis] ; XIAOMING XU [États-Unis] ; Kiira Ratia [États-Unis] ; WENTAO FU [États-Unis] ; Katherine V. Houser [États-Unis] ; Susan C. Baker [États-Unis] ; Michael E. Johnson [États-Unis] ; Andrew D. Mesecar [États-Unis]Source :
- Bioorganic & medicinal chemistry letters : (Print) [ 0960-894X ] ; 2007.
Descripteurs français
- Pascal (Inist)
- Relation structure activité, Synthèse chimique, Antiviral, Composé peptidomimétique, Virus syndrome respiratoire aigu sévère, Inhibiteur protease, Structure cristalline, Composé non peptide, Composé aliphatique, Lactame, In vitro, Modèle moléculaire, Complexe enzyme inhibiteur, Aminoester, Composé éthylénique, Liaison hydrogène, Inhibiteur enzyme, Peptidases, Modélisation, Diffraction RX, Structure moléculaire, Pent-2-énoïque acide dérivé, Pyrrolidin-2-one dérivé, Hex-4-énoïque acide dérivé, Sérine dérivé.
English descriptors
- KwdEn :
- Aliphatic compound, Aminoester, Antiviral, Chemical synthesis, Crystalline structure, Enzyme inhibitor, Ethylenic compound, Hydrogen bond, In vitro, Inhibitor enzyme complex, Lactam, Modeling, Molecular model, Molecular structure, Non peptide compound, Peptidases, Peptidomimetic compound, Protease inhibitor, Severe acute respiratory syndrome virus, Structure activity relation, X ray diffraction.
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.
Affiliations:
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Pascal:08-0100536Le document en format XML
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<term>Enzyme inhibitor</term>
<term>Ethylenic compound</term>
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<term>Inhibitor enzyme complex</term>
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<term>Modeling</term>
<term>Molecular model</term>
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<term>Synthèse chimique</term>
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<term>Composé peptidomimétique</term>
<term>Virus syndrome respiratoire aigu sévère</term>
<term>Inhibiteur protease</term>
<term>Structure cristalline</term>
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<front><div type="abstract" xml:lang="en">-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 P<sub>4</sub>
-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.</div>
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<s5>354000143466890260</s5>
</fA43>
<fA44><s0>0000</s0>
<s1>© 2008 INIST-CNRS. All rights reserved.</s1>
</fA44>
<fA45><s0>20 ref.</s0>
</fA45>
<fA47 i1="01" i2="1"><s0>08-0100536</s0>
</fA47>
<fA60><s1>P</s1>
</fA60>
<fA61><s0>A</s0>
</fA61>
<fA64 i1="01" i2="1"><s0>Bioorganic & medicinal chemistry letters : (Print)</s0>
</fA64>
<fA66 i1="01"><s0>GBR</s0>
</fA66>
<fC01 i1="01" l="ENG"><s0>-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 P<sub>4</sub>
-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.</s0>
</fC01>
<fC02 i1="01" i2="X"><s0>002B02S05</s0>
</fC02>
<fC03 i1="01" i2="X" l="FRE"><s0>Relation structure activité</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG"><s0>Structure activity relation</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA"><s0>Relación estructura actividad</s0>
<s5>01</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE"><s0>Synthèse chimique</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG"><s0>Chemical synthesis</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="SPA"><s0>Síntesis química</s0>
<s5>02</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE"><s0>Antiviral</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG"><s0>Antiviral</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA"><s0>Antiviral</s0>
<s5>03</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE"><s0>Composé peptidomimétique</s0>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG"><s0>Peptidomimetic compound</s0>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA"><s0>Compuesto peptidomimético</s0>
<s5>04</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE"><s0>Virus syndrome respiratoire aigu sévère</s0>
<s2>NW</s2>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG"><s0>Severe acute respiratory syndrome virus</s0>
<s2>NW</s2>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA"><s0>Severe acute respiratory syndrome virus</s0>
<s2>NW</s2>
<s5>05</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE"><s0>Inhibiteur protease</s0>
<s2>FR</s2>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG"><s0>Protease inhibitor</s0>
<s2>FR</s2>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="SPA"><s0>Inhibidor proteasa</s0>
<s2>FR</s2>
<s5>06</s5>
</fC03>
<fC03 i1="07" i2="X" l="FRE"><s0>Structure cristalline</s0>
<s5>07</s5>
</fC03>
<fC03 i1="07" i2="X" l="ENG"><s0>Crystalline structure</s0>
<s5>07</s5>
</fC03>
<fC03 i1="07" i2="X" l="SPA"><s0>Estructura cristalina</s0>
<s5>07</s5>
</fC03>
<fC03 i1="08" i2="X" l="FRE"><s0>Composé non peptide</s0>
<s5>08</s5>
</fC03>
<fC03 i1="08" i2="X" l="ENG"><s0>Non peptide compound</s0>
<s5>08</s5>
</fC03>
<fC03 i1="08" i2="X" l="SPA"><s0>Compuesto no péptido</s0>
<s5>08</s5>
</fC03>
<fC03 i1="09" i2="X" l="FRE"><s0>Composé aliphatique</s0>
<s5>09</s5>
</fC03>
<fC03 i1="09" i2="X" l="ENG"><s0>Aliphatic compound</s0>
<s5>09</s5>
</fC03>
<fC03 i1="09" i2="X" l="SPA"><s0>Compuesto alifático</s0>
<s5>09</s5>
</fC03>
<fC03 i1="10" i2="X" l="FRE"><s0>Lactame</s0>
<s5>10</s5>
</fC03>
<fC03 i1="10" i2="X" l="ENG"><s0>Lactam</s0>
<s5>10</s5>
</fC03>
<fC03 i1="10" i2="X" l="SPA"><s0>Lactamo</s0>
<s5>10</s5>
</fC03>
<fC03 i1="11" i2="X" l="FRE"><s0>In vitro</s0>
<s5>11</s5>
</fC03>
<fC03 i1="11" i2="X" l="ENG"><s0>In vitro</s0>
<s5>11</s5>
</fC03>
<fC03 i1="11" i2="X" l="SPA"><s0>In vitro</s0>
<s5>11</s5>
</fC03>
<fC03 i1="12" i2="X" l="FRE"><s0>Modèle moléculaire</s0>
<s5>12</s5>
</fC03>
<fC03 i1="12" i2="X" l="ENG"><s0>Molecular model</s0>
<s5>12</s5>
</fC03>
<fC03 i1="12" i2="X" l="SPA"><s0>Modelo molecular</s0>
<s5>12</s5>
</fC03>
<fC03 i1="13" i2="X" l="FRE"><s0>Complexe enzyme inhibiteur</s0>
<s5>13</s5>
</fC03>
<fC03 i1="13" i2="X" l="ENG"><s0>Inhibitor enzyme complex</s0>
<s5>13</s5>
</fC03>
<fC03 i1="13" i2="X" l="SPA"><s0>Complejo enzima inhibidor</s0>
<s5>13</s5>
</fC03>
<fC03 i1="14" i2="X" l="FRE"><s0>Aminoester</s0>
<s5>14</s5>
</fC03>
<fC03 i1="14" i2="X" l="ENG"><s0>Aminoester</s0>
<s5>14</s5>
</fC03>
<fC03 i1="14" i2="X" l="SPA"><s0>Aminoester</s0>
<s5>14</s5>
</fC03>
<fC03 i1="15" i2="X" l="FRE"><s0>Composé éthylénique</s0>
<s5>15</s5>
</fC03>
<fC03 i1="15" i2="X" l="ENG"><s0>Ethylenic compound</s0>
<s5>15</s5>
</fC03>
<fC03 i1="15" i2="X" l="SPA"><s0>Compuesto etilénico</s0>
<s5>15</s5>
</fC03>
<fC03 i1="16" i2="X" l="FRE"><s0>Liaison hydrogène</s0>
<s5>16</s5>
</fC03>
<fC03 i1="16" i2="X" l="ENG"><s0>Hydrogen bond</s0>
<s5>16</s5>
</fC03>
<fC03 i1="16" i2="X" l="SPA"><s0>Enlace hidrógeno</s0>
<s5>16</s5>
</fC03>
<fC03 i1="17" i2="X" l="FRE"><s0>Inhibiteur enzyme</s0>
<s5>32</s5>
</fC03>
<fC03 i1="17" i2="X" l="ENG"><s0>Enzyme inhibitor</s0>
<s5>32</s5>
</fC03>
<fC03 i1="17" i2="X" l="SPA"><s0>Inhibidor enzima</s0>
<s5>32</s5>
</fC03>
<fC03 i1="18" i2="X" l="FRE"><s0>Peptidases</s0>
<s2>FE</s2>
<s5>33</s5>
</fC03>
<fC03 i1="18" i2="X" l="ENG"><s0>Peptidases</s0>
<s2>FE</s2>
<s5>33</s5>
</fC03>
<fC03 i1="18" i2="X" l="SPA"><s0>Peptidases</s0>
<s2>FE</s2>
<s5>33</s5>
</fC03>
<fC03 i1="19" i2="X" l="FRE"><s0>Modélisation</s0>
<s5>35</s5>
</fC03>
<fC03 i1="19" i2="X" l="ENG"><s0>Modeling</s0>
<s5>35</s5>
</fC03>
<fC03 i1="19" i2="X" l="SPA"><s0>Modelización</s0>
<s5>35</s5>
</fC03>
<fC03 i1="20" i2="X" l="FRE"><s0>Diffraction RX</s0>
<s5>36</s5>
</fC03>
<fC03 i1="20" i2="X" l="ENG"><s0>X ray diffraction</s0>
<s5>36</s5>
</fC03>
<fC03 i1="20" i2="X" l="SPA"><s0>Difracción RX</s0>
<s5>36</s5>
</fC03>
<fC03 i1="21" i2="X" l="FRE"><s0>Structure moléculaire</s0>
<s5>37</s5>
</fC03>
<fC03 i1="21" i2="X" l="ENG"><s0>Molecular structure</s0>
<s5>37</s5>
</fC03>
<fC03 i1="21" i2="X" l="SPA"><s0>Estructura molecular</s0>
<s5>37</s5>
</fC03>
<fC03 i1="22" i2="X" l="FRE"><s0>Pent-2-énoïque acide dérivé</s0>
<s2>NK</s2>
<s4>INC</s4>
<s5>76</s5>
</fC03>
<fC03 i1="23" i2="X" l="FRE"><s0>Pyrrolidin-2-one dérivé</s0>
<s2>NK</s2>
<s4>INC</s4>
<s5>77</s5>
</fC03>
<fC03 i1="24" i2="X" l="FRE"><s0>Hex-4-énoïque acide dérivé</s0>
<s2>NK</s2>
<s4>INC</s4>
<s5>78</s5>
</fC03>
<fC03 i1="25" i2="X" l="FRE"><s0>Sérine dérivé</s0>
<s2>NK</s2>
<s4>INC</s4>
<s5>79</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE"><s0>Coronavirus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="01" i2="X" l="ENG"><s0>Coronavirus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="01" i2="X" l="SPA"><s0>Coronavirus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="02" i2="X" l="FRE"><s0>Coronaviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="02" i2="X" l="ENG"><s0>Coronaviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="02" i2="X" l="SPA"><s0>Coronaviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="FRE"><s0>Nidovirales</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="ENG"><s0>Nidovirales</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="SPA"><s0>Nidovirales</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="04" i2="X" l="FRE"><s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="04" i2="X" l="ENG"><s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="04" i2="X" l="SPA"><s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="05" i2="X" l="FRE"><s0>Hydrolases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="05" i2="X" l="ENG"><s0>Hydrolases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="05" i2="X" l="SPA"><s0>Hydrolases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="06" i2="X" l="FRE"><s0>Enzyme</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="06" i2="X" l="ENG"><s0>Enzyme</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="06" i2="X" l="SPA"><s0>Enzima</s0>
<s2>FE</s2>
</fC07>
<fN21><s1>056</s1>
</fN21>
</pA>
</standard>
</inist>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Illinois</li>
<li>Indiana</li>
</region>
<settlement><li>Chicago</li>
</settlement>
<orgName><li>Université de Chicago</li>
<li>Université de l'Illinois à Chicago</li>
</orgName>
</list>
<tree><country name="États-Unis"><region name="Indiana"><name sortKey="Ghosh, Arun K" sort="Ghosh, Arun K" uniqKey="Ghosh A" first="Arun K." last="Ghosh">Arun K. Ghosh</name>
</region>
<name sortKey="Baker, Susan C" sort="Baker, Susan C" uniqKey="Baker S" first="Susan C." last="Baker">Susan C. Baker</name>
<name sortKey="Grum Tokars, Valerie" sort="Grum Tokars, Valerie" uniqKey="Grum Tokars V" first="Valerie" last="Grum-Tokars">Valerie Grum-Tokars</name>
<name sortKey="Houser, Katherine V" sort="Houser, Katherine V" uniqKey="Houser K" first="Katherine V." last="Houser">Katherine V. Houser</name>
<name sortKey="Johnson, Michael E" sort="Johnson, Michael E" uniqKey="Johnson M" first="Michael E." last="Johnson">Michael E. Johnson</name>
<name sortKey="Kai Xi" sort="Kai Xi" uniqKey="Kai Xi" last="Kai Xi">KAI XI</name>
<name sortKey="Mesecar, Andrew D" sort="Mesecar, Andrew D" uniqKey="Mesecar A" first="Andrew D." last="Mesecar">Andrew D. Mesecar</name>
<name sortKey="Ratia, Kiira" sort="Ratia, Kiira" uniqKey="Ratia K" first="Kiira" last="Ratia">Kiira Ratia</name>
<name sortKey="Wentao Fu" sort="Wentao Fu" uniqKey="Wentao Fu" last="Wentao Fu">WENTAO FU</name>
<name sortKey="Xiaoming Xu" sort="Xiaoming Xu" uniqKey="Xiaoming Xu" last="Xiaoming Xu">XIAOMING XU</name>
</country>
</tree>
</affiliations>
</record>
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