Molecular Modeling and 3D-QSAR Studies on the Interaction Mechanism of Tripeptidyl Thrombin Inhibitors with Human α-Thrombin
The mechanism of inhibition of peptidyl inhibitors with thrombin was studied using molecular modeling, molecular mechanics, and CoMFA statistical analysis. A new procedure for the elucidation of binding conformations, BCSPL, is described and was employed to obtain the binding conformers of a series...
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| Veröffentlicht in: | Journal of medicinal chemistry 1997-09, Vol.40 (19), p.3085-3090 |
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| container_end_page | 3090 |
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| container_issue | 19 |
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| container_title | Journal of medicinal chemistry |
| container_volume | 40 |
| creator | Jiang, Hualiang Chen, Kaixian Tang, Yun Chen, Jianzhong Li, Quan Wang, Qinmi Ji, Ruyun |
| description | The mechanism of inhibition of peptidyl inhibitors with thrombin was studied using molecular modeling, molecular mechanics, and CoMFA statistical analysis. A new procedure for the elucidation of binding conformations, BCSPL, is described and was employed to obtain the binding conformers of a series of 18 tripeptidyl thrombin inhibitors. Energetic studies and QSAR analysis of the BCSPL-derived conformers indicated a modest correlation between the calculated binding energies of the title compounds and their inhibitory activities to human α-thrombin. CoMFA analysis of the BCSPL alignment resulted in a satisfactory model of the thrombin active site. |
| doi_str_mv | 10.1021/jm960309m |
| format | Article |
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A new procedure for the elucidation of binding conformations, BCSPL, is described and was employed to obtain the binding conformers of a series of 18 tripeptidyl thrombin inhibitors. Energetic studies and QSAR analysis of the BCSPL-derived conformers indicated a modest correlation between the calculated binding energies of the title compounds and their inhibitory activities to human α-thrombin. CoMFA analysis of the BCSPL alignment resulted in a satisfactory model of the thrombin active site.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm960309m</identifier><identifier>PMID: 9301672</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Antithrombins - chemistry ; Antithrombins - pharmacology ; Binding Sites ; Biological and medical sciences ; Blood. Blood coagulation. Reticuloendothelial system ; Calorimetry ; Computer Graphics ; Computer Simulation ; Crystallography, X-Ray ; Humans ; Kinetics ; Medical sciences ; Models, Molecular ; Oligopeptides - chemistry ; Oligopeptides - pharmacology ; Pharmacology. Drug treatments ; Protein Conformation ; Structure-Activity Relationship ; Thermodynamics ; Thrombin - antagonists & inhibitors ; Thrombin - chemistry</subject><ispartof>Journal of medicinal chemistry, 1997-09, Vol.40 (19), p.3085-3090</ispartof><rights>Copyright © 1997 American Chemical Society</rights><rights>1997 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a377t-317cb244bbf34f8de499b0e38d844633209b183330106e5a27a4e9b31dc711223</citedby><cites>FETCH-LOGICAL-a377t-317cb244bbf34f8de499b0e38d844633209b183330106e5a27a4e9b31dc711223</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm960309m$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm960309m$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2821694$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9301672$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jiang, Hualiang</creatorcontrib><creatorcontrib>Chen, Kaixian</creatorcontrib><creatorcontrib>Tang, Yun</creatorcontrib><creatorcontrib>Chen, Jianzhong</creatorcontrib><creatorcontrib>Li, Quan</creatorcontrib><creatorcontrib>Wang, Qinmi</creatorcontrib><creatorcontrib>Ji, Ruyun</creatorcontrib><title>Molecular Modeling and 3D-QSAR Studies on the Interaction Mechanism of Tripeptidyl Thrombin Inhibitors with Human α-Thrombin</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>The mechanism of inhibition of peptidyl inhibitors with thrombin was studied using molecular modeling, molecular mechanics, and CoMFA statistical analysis. A new procedure for the elucidation of binding conformations, BCSPL, is described and was employed to obtain the binding conformers of a series of 18 tripeptidyl thrombin inhibitors. Energetic studies and QSAR analysis of the BCSPL-derived conformers indicated a modest correlation between the calculated binding energies of the title compounds and their inhibitory activities to human α-thrombin. CoMFA analysis of the BCSPL alignment resulted in a satisfactory model of the thrombin active site.</description><subject>Antithrombins - chemistry</subject><subject>Antithrombins - pharmacology</subject><subject>Binding Sites</subject><subject>Biological and medical sciences</subject><subject>Blood. Blood coagulation. Reticuloendothelial system</subject><subject>Calorimetry</subject><subject>Computer Graphics</subject><subject>Computer Simulation</subject><subject>Crystallography, X-Ray</subject><subject>Humans</subject><subject>Kinetics</subject><subject>Medical sciences</subject><subject>Models, Molecular</subject><subject>Oligopeptides - chemistry</subject><subject>Oligopeptides - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Protein Conformation</subject><subject>Structure-Activity Relationship</subject><subject>Thermodynamics</subject><subject>Thrombin - antagonists & inhibitors</subject><subject>Thrombin - chemistry</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0MtuEzEUBmALUZVQWPAASF5AJRYDvsUeL6tQaKuGWwILNpbH42EcZuxgewRd9KH6IjwTRglZsbKO_k9Hxz8ATzB6iRHBrzaj5IgiOd4DMzwnqGI1YvfBDCFCKsIJfQAeprRBCFFM6DE4lhRhLsgM3C7DYM006AiXobWD89-g9i2kr6uPq7NPcJWn1tkEg4e5t_DSZxu1ya7MS2t67V0aYejgOrqt3WbX3gxw3ccwNs4X3bvG5RAT_OlyDy-mUXv4-676Jx6Bo04PyT7evyfg85vz9eKiun7_9nJxdl1pKkSuKBamIYw1TUdZV7eWSdkgS-u2ZoxTSpBscE1p-RTidq6J0MzKhuLWCIwJoSfgdLd3G8OPyaasRpeMHQbtbZiSEpLUnMt5gS920MSQUrSd2kY36nijMFJ_q1aHqot9ul86NaNtD3Lfbcmf7XOdjB66qL1x6cBITTCXrLBqx1zK9tch1vG74oKKuVp_WKl3X5H4Qq8WChf_fOe1SWoTpuhLc_857w8956Ew</recordid><startdate>19970912</startdate><enddate>19970912</enddate><creator>Jiang, Hualiang</creator><creator>Chen, Kaixian</creator><creator>Tang, Yun</creator><creator>Chen, Jianzhong</creator><creator>Li, Quan</creator><creator>Wang, Qinmi</creator><creator>Ji, Ruyun</creator><general>American Chemical Society</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19970912</creationdate><title>Molecular Modeling and 3D-QSAR Studies on the Interaction Mechanism of Tripeptidyl Thrombin Inhibitors with Human α-Thrombin</title><author>Jiang, Hualiang ; Chen, Kaixian ; Tang, Yun ; Chen, Jianzhong ; Li, Quan ; Wang, Qinmi ; Ji, Ruyun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a377t-317cb244bbf34f8de499b0e38d844633209b183330106e5a27a4e9b31dc711223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Antithrombins - chemistry</topic><topic>Antithrombins - pharmacology</topic><topic>Binding Sites</topic><topic>Biological and medical sciences</topic><topic>Blood. Blood coagulation. Reticuloendothelial system</topic><topic>Calorimetry</topic><topic>Computer Graphics</topic><topic>Computer Simulation</topic><topic>Crystallography, X-Ray</topic><topic>Humans</topic><topic>Kinetics</topic><topic>Medical sciences</topic><topic>Models, Molecular</topic><topic>Oligopeptides - chemistry</topic><topic>Oligopeptides - pharmacology</topic><topic>Pharmacology. 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Med. Chem</addtitle><date>1997-09-12</date><risdate>1997</risdate><volume>40</volume><issue>19</issue><spage>3085</spage><epage>3090</epage><pages>3085-3090</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>The mechanism of inhibition of peptidyl inhibitors with thrombin was studied using molecular modeling, molecular mechanics, and CoMFA statistical analysis. A new procedure for the elucidation of binding conformations, BCSPL, is described and was employed to obtain the binding conformers of a series of 18 tripeptidyl thrombin inhibitors. Energetic studies and QSAR analysis of the BCSPL-derived conformers indicated a modest correlation between the calculated binding energies of the title compounds and their inhibitory activities to human α-thrombin. CoMFA analysis of the BCSPL alignment resulted in a satisfactory model of the thrombin active site.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>9301672</pmid><doi>10.1021/jm960309m</doi><tpages>6</tpages></addata></record> |
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| identifier | ISSN: 0022-2623 |
| ispartof | Journal of medicinal chemistry, 1997-09, Vol.40 (19), p.3085-3090 |
| issn | 0022-2623 1520-4804 |
| language | eng |
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| source | ACS Publications; MEDLINE |
| subjects | Antithrombins - chemistry Antithrombins - pharmacology Binding Sites Biological and medical sciences Blood. Blood coagulation. Reticuloendothelial system Calorimetry Computer Graphics Computer Simulation Crystallography, X-Ray Humans Kinetics Medical sciences Models, Molecular Oligopeptides - chemistry Oligopeptides - pharmacology Pharmacology. Drug treatments Protein Conformation Structure-Activity Relationship Thermodynamics Thrombin - antagonists & inhibitors Thrombin - chemistry |
| title | Molecular Modeling and 3D-QSAR Studies on the Interaction Mechanism of Tripeptidyl Thrombin Inhibitors with Human α-Thrombin |
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