A Unified and Quantitative Receptor Model for the Microtubule Binding of Paclitaxel and Epothilone
Paclitaxel and epothilone represent the two major classes of antimicrotubule agents that promote tubulin polymerization and, presumably, mitotic arrest during cell division. A common minireceptor binding site model at β-tubulin has been constructed for these structurally divergent compounds. Utilizi...
Gespeichert in:
| Veröffentlicht in: | Organic letters 1999-07, Vol.1 (1), p.43-46 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 46 |
|---|---|
| container_issue | 1 |
| container_start_page | 43 |
| container_title | Organic letters |
| container_volume | 1 |
| creator | Wang, Minmin Xia, Xiaoyang Kim, Yohan Hwang, David Jansen, Johanna M Botta, Maurizio Liotta, Dennis C Snyder, James P |
| description | Paclitaxel and epothilone represent the two major classes of antimicrotubule agents that promote tubulin polymerization and, presumably, mitotic arrest during cell division. A common minireceptor binding site model at β-tubulin has been constructed for these structurally divergent compounds. Utilizing 20 amino acids identified in photoaffinity labeling experiments, the 3-D model correlates measured and predicted K i's with r = 0.99 and rms(ΔG calc − ΔG exp) = 0.2 kcal/mol. In addition, the model predicts the affinity of compounds not used in the training set and explains much of the SAR for the paclitaxel and epothilone families. |
| doi_str_mv | 10.1021/ol990521v |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_69478560</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>69478560</sourcerecordid><originalsourceid>FETCH-LOGICAL-a377t-cbdef9aa13022ac715fb7fe9cded65565bf62a6ac505887cbdb81e1e8ff9848f3</originalsourceid><addsrcrecordid>eNptkEtPwzAQhC0EoqVw4A8gX0DiELCTOnGOpSoPiYqH6DlynDV15cYhdir497hKVXHgtLOrb0eaQeickhtKYnprTZ4TFtPNARpSFidRFrbDvU7JAJ04tyKEhkt-jAaU8DhmCRmicoIXtVYaKizqCr91ovbaC683gN9BQuNti-e2AoNVUH4JeK5la31Xdgbwna4rXX9iq_CrkCZ8fgdy6zRrrF9qY2s4RUdKGAdnuzlCi_vZx_Qxen55eJpOniORZJmPZFmByoWgCYljITPKVJkpyGUFVcpYykqVxiIVkhHGeRbwklOgwJXK-ZirZISuet-mtV8dOF-stZNgjKjBdq5I83HGWUoCeN2DIYdzLaiiafVatD8FJcW20GJfaGAvdqZduYbqD9k3GIDLHhDSFSvbtXXI-I_RL1c6fi8</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>69478560</pqid></control><display><type>article</type><title>A Unified and Quantitative Receptor Model for the Microtubule Binding of Paclitaxel and Epothilone</title><source>MEDLINE</source><source>American Chemical Society Journals</source><creator>Wang, Minmin ; Xia, Xiaoyang ; Kim, Yohan ; Hwang, David ; Jansen, Johanna M ; Botta, Maurizio ; Liotta, Dennis C ; Snyder, James P</creator><creatorcontrib>Wang, Minmin ; Xia, Xiaoyang ; Kim, Yohan ; Hwang, David ; Jansen, Johanna M ; Botta, Maurizio ; Liotta, Dennis C ; Snyder, James P</creatorcontrib><description>Paclitaxel and epothilone represent the two major classes of antimicrotubule agents that promote tubulin polymerization and, presumably, mitotic arrest during cell division. A common minireceptor binding site model at β-tubulin has been constructed for these structurally divergent compounds. Utilizing 20 amino acids identified in photoaffinity labeling experiments, the 3-D model correlates measured and predicted K i's with r = 0.99 and rms(ΔG calc − ΔG exp) = 0.2 kcal/mol. In addition, the model predicts the affinity of compounds not used in the training set and explains much of the SAR for the paclitaxel and epothilone families.</description><identifier>ISSN: 1523-7060</identifier><identifier>EISSN: 1523-7052</identifier><identifier>DOI: 10.1021/ol990521v</identifier><identifier>PMID: 10822530</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Antineoplastic Agents - chemistry ; Antineoplastic Agents - metabolism ; Epothilones ; Epoxy Compounds - chemistry ; Epoxy Compounds - metabolism ; Magnetic Resonance Spectroscopy ; Microtubules - chemistry ; Microtubules - metabolism ; Models, Molecular ; Monte Carlo Method ; Paclitaxel - chemistry ; Paclitaxel - metabolism ; Protein Binding ; Receptors, Drug - chemistry ; Receptors, Drug - metabolism ; Structure-Activity Relationship ; Thiazoles - chemistry ; Thiazoles - metabolism ; Tubulin - chemistry ; Tubulin - metabolism</subject><ispartof>Organic letters, 1999-07, Vol.1 (1), p.43-46</ispartof><rights>Copyright © 1999 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a377t-cbdef9aa13022ac715fb7fe9cded65565bf62a6ac505887cbdb81e1e8ff9848f3</citedby><cites>FETCH-LOGICAL-a377t-cbdef9aa13022ac715fb7fe9cded65565bf62a6ac505887cbdb81e1e8ff9848f3</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/ol990521v$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/ol990521v$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10822530$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Minmin</creatorcontrib><creatorcontrib>Xia, Xiaoyang</creatorcontrib><creatorcontrib>Kim, Yohan</creatorcontrib><creatorcontrib>Hwang, David</creatorcontrib><creatorcontrib>Jansen, Johanna M</creatorcontrib><creatorcontrib>Botta, Maurizio</creatorcontrib><creatorcontrib>Liotta, Dennis C</creatorcontrib><creatorcontrib>Snyder, James P</creatorcontrib><title>A Unified and Quantitative Receptor Model for the Microtubule Binding of Paclitaxel and Epothilone</title><title>Organic letters</title><addtitle>Org. Lett</addtitle><description>Paclitaxel and epothilone represent the two major classes of antimicrotubule agents that promote tubulin polymerization and, presumably, mitotic arrest during cell division. A common minireceptor binding site model at β-tubulin has been constructed for these structurally divergent compounds. Utilizing 20 amino acids identified in photoaffinity labeling experiments, the 3-D model correlates measured and predicted K i's with r = 0.99 and rms(ΔG calc − ΔG exp) = 0.2 kcal/mol. In addition, the model predicts the affinity of compounds not used in the training set and explains much of the SAR for the paclitaxel and epothilone families.</description><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - metabolism</subject><subject>Epothilones</subject><subject>Epoxy Compounds - chemistry</subject><subject>Epoxy Compounds - metabolism</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Microtubules - chemistry</subject><subject>Microtubules - metabolism</subject><subject>Models, Molecular</subject><subject>Monte Carlo Method</subject><subject>Paclitaxel - chemistry</subject><subject>Paclitaxel - metabolism</subject><subject>Protein Binding</subject><subject>Receptors, Drug - chemistry</subject><subject>Receptors, Drug - metabolism</subject><subject>Structure-Activity Relationship</subject><subject>Thiazoles - chemistry</subject><subject>Thiazoles - metabolism</subject><subject>Tubulin - chemistry</subject><subject>Tubulin - metabolism</subject><issn>1523-7060</issn><issn>1523-7052</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkEtPwzAQhC0EoqVw4A8gX0DiELCTOnGOpSoPiYqH6DlynDV15cYhdir497hKVXHgtLOrb0eaQeickhtKYnprTZ4TFtPNARpSFidRFrbDvU7JAJ04tyKEhkt-jAaU8DhmCRmicoIXtVYaKizqCr91ovbaC683gN9BQuNti-e2AoNVUH4JeK5la31Xdgbwna4rXX9iq_CrkCZ8fgdy6zRrrF9qY2s4RUdKGAdnuzlCi_vZx_Qxen55eJpOniORZJmPZFmByoWgCYljITPKVJkpyGUFVcpYykqVxiIVkhHGeRbwklOgwJXK-ZirZISuet-mtV8dOF-stZNgjKjBdq5I83HGWUoCeN2DIYdzLaiiafVatD8FJcW20GJfaGAvdqZduYbqD9k3GIDLHhDSFSvbtXXI-I_RL1c6fi8</recordid><startdate>19990715</startdate><enddate>19990715</enddate><creator>Wang, Minmin</creator><creator>Xia, Xiaoyang</creator><creator>Kim, Yohan</creator><creator>Hwang, David</creator><creator>Jansen, Johanna M</creator><creator>Botta, Maurizio</creator><creator>Liotta, Dennis C</creator><creator>Snyder, James P</creator><general>American Chemical Society</general><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>19990715</creationdate><title>A Unified and Quantitative Receptor Model for the Microtubule Binding of Paclitaxel and Epothilone</title><author>Wang, Minmin ; Xia, Xiaoyang ; Kim, Yohan ; Hwang, David ; Jansen, Johanna M ; Botta, Maurizio ; Liotta, Dennis C ; Snyder, James P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a377t-cbdef9aa13022ac715fb7fe9cded65565bf62a6ac505887cbdb81e1e8ff9848f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - metabolism</topic><topic>Epothilones</topic><topic>Epoxy Compounds - chemistry</topic><topic>Epoxy Compounds - metabolism</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Microtubules - chemistry</topic><topic>Microtubules - metabolism</topic><topic>Models, Molecular</topic><topic>Monte Carlo Method</topic><topic>Paclitaxel - chemistry</topic><topic>Paclitaxel - metabolism</topic><topic>Protein Binding</topic><topic>Receptors, Drug - chemistry</topic><topic>Receptors, Drug - metabolism</topic><topic>Structure-Activity Relationship</topic><topic>Thiazoles - chemistry</topic><topic>Thiazoles - metabolism</topic><topic>Tubulin - chemistry</topic><topic>Tubulin - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Minmin</creatorcontrib><creatorcontrib>Xia, Xiaoyang</creatorcontrib><creatorcontrib>Kim, Yohan</creatorcontrib><creatorcontrib>Hwang, David</creatorcontrib><creatorcontrib>Jansen, Johanna M</creatorcontrib><creatorcontrib>Botta, Maurizio</creatorcontrib><creatorcontrib>Liotta, Dennis C</creatorcontrib><creatorcontrib>Snyder, James P</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Organic letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Minmin</au><au>Xia, Xiaoyang</au><au>Kim, Yohan</au><au>Hwang, David</au><au>Jansen, Johanna M</au><au>Botta, Maurizio</au><au>Liotta, Dennis C</au><au>Snyder, James P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Unified and Quantitative Receptor Model for the Microtubule Binding of Paclitaxel and Epothilone</atitle><jtitle>Organic letters</jtitle><addtitle>Org. Lett</addtitle><date>1999-07-15</date><risdate>1999</risdate><volume>1</volume><issue>1</issue><spage>43</spage><epage>46</epage><pages>43-46</pages><issn>1523-7060</issn><eissn>1523-7052</eissn><abstract>Paclitaxel and epothilone represent the two major classes of antimicrotubule agents that promote tubulin polymerization and, presumably, mitotic arrest during cell division. A common minireceptor binding site model at β-tubulin has been constructed for these structurally divergent compounds. Utilizing 20 amino acids identified in photoaffinity labeling experiments, the 3-D model correlates measured and predicted K i's with r = 0.99 and rms(ΔG calc − ΔG exp) = 0.2 kcal/mol. In addition, the model predicts the affinity of compounds not used in the training set and explains much of the SAR for the paclitaxel and epothilone families.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>10822530</pmid><doi>10.1021/ol990521v</doi><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1523-7060 |
| ispartof | Organic letters, 1999-07, Vol.1 (1), p.43-46 |
| issn | 1523-7060 1523-7052 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_69478560 |
| source | MEDLINE; American Chemical Society Journals |
| subjects | Antineoplastic Agents - chemistry Antineoplastic Agents - metabolism Epothilones Epoxy Compounds - chemistry Epoxy Compounds - metabolism Magnetic Resonance Spectroscopy Microtubules - chemistry Microtubules - metabolism Models, Molecular Monte Carlo Method Paclitaxel - chemistry Paclitaxel - metabolism Protein Binding Receptors, Drug - chemistry Receptors, Drug - metabolism Structure-Activity Relationship Thiazoles - chemistry Thiazoles - metabolism Tubulin - chemistry Tubulin - metabolism |
| title | A Unified and Quantitative Receptor Model for the Microtubule Binding of Paclitaxel and Epothilone |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-27T07%3A43%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20Unified%20and%20Quantitative%20Receptor%20Model%20for%20the%20Microtubule%20Binding%20of%20Paclitaxel%20and%20Epothilone&rft.jtitle=Organic%20letters&rft.au=Wang,%20Minmin&rft.date=1999-07-15&rft.volume=1&rft.issue=1&rft.spage=43&rft.epage=46&rft.pages=43-46&rft.issn=1523-7060&rft.eissn=1523-7052&rft_id=info:doi/10.1021/ol990521v&rft_dat=%3Cproquest_cross%3E69478560%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=69478560&rft_id=info:pmid/10822530&rfr_iscdi=true |