Design, synthesis, and kinetic evaluation of high-affinity FKBP ligands and the X-ray crystal structures of their complexes with FKBP12
The design and synthesis of high-affinity FKBP12 ligands is described. These compounds potently inhibit the cis-trans-peptidylprolyl isomerase (rotamase) activity catalyzed by FKBP12 with inhibition constants (K sub(i,app)) as low as 1 nM, yet they possess remarkable structural simplicity relative t...
Gespeichert in:
| Veröffentlicht in: | Journal of the American Chemical Society 1993-11, Vol.115 (22), p.9925-9938 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 9938 |
|---|---|
| container_issue | 22 |
| container_start_page | 9925 |
| container_title | Journal of the American Chemical Society |
| container_volume | 115 |
| creator | Holt, Dennis A Luengo, Juan I Yamashita, Dennis S Oh, Hye Ja Konialian, Arda L Yen, Hwa Kwo Rozamus, Leonard W Brandt, Martin Bossard, Mary J |
| description | The design and synthesis of high-affinity FKBP12 ligands is described. These compounds potently inhibit the cis-trans-peptidylprolyl isomerase (rotamase) activity catalyzed by FKBP12 with inhibition constants (K sub(i,app)) as low as 1 nM, yet they possess remarkable structural simplicity relative to FK506 and rapamycin, from which they are conceptually derived. The atomic structures of three FKBP12-ligand complexes and of one unbound ligand were determined by X-ray crystallography and are compared to the FKBP12-FK506 and FKBP12-rapamycin complexes. |
| doi_str_mv | 10.1021/ja00075a008 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_16629967</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>16629967</sourcerecordid><originalsourceid>FETCH-LOGICAL-a361t-2cfae90092036ca2cbf3274572a0954680ce4ee34661c553ecddaf87e436767d3</originalsourceid><addsrcrecordid>eNptkE1uFDEQhS0EEkNgxQW8QLAgDf5p291LEgigRCKCILGzCo8940mPe-JyQ_oEXBsnE0Us2Ljsqu89lx4hzzl7w5ngbzfAGDOqnt0DsuBKsEZxoR-SRe2LxnRaPiZPEDf12YqOL8if9x7jKh1SnFNZ1zseUkhLehmTL9FR_wuGCUocEx0DXcfVuoEQYoplpienR-d0iKvK462oGtAfTYaZujxjgYFiyZMrU_Z4I6_zmKkbt7vBX9fW71jWty5cPCWPAgzon93VA_L95MPF8afm7MvHz8fvzhqQmpdGuAC-Z6wXTGoHwv0MUphWGQGsV63umPOt97LVmjulpHfLJYTO-FZqo81SHpCXe99dHq8mj8VuIzo_DJD8OKHlWou-16aCr_egyyNi9sHuctxCni1n9iZs-0_YlX5xZwvoYAgZkot4L5GdEabrK9bssYjFX9-PIV_a-qVR9uL8mz3tvvZCKmOPKv9qz4NDuxmnnGo2_13gLxXCmjE</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>16629967</pqid></control><display><type>article</type><title>Design, synthesis, and kinetic evaluation of high-affinity FKBP ligands and the X-ray crystal structures of their complexes with FKBP12</title><source>ACS Publications</source><creator>Holt, Dennis A ; Luengo, Juan I ; Yamashita, Dennis S ; Oh, Hye Ja ; Konialian, Arda L ; Yen, Hwa Kwo ; Rozamus, Leonard W ; Brandt, Martin ; Bossard, Mary J</creator><creatorcontrib>Holt, Dennis A ; Luengo, Juan I ; Yamashita, Dennis S ; Oh, Hye Ja ; Konialian, Arda L ; Yen, Hwa Kwo ; Rozamus, Leonard W ; Brandt, Martin ; Bossard, Mary J</creatorcontrib><description>The design and synthesis of high-affinity FKBP12 ligands is described. These compounds potently inhibit the cis-trans-peptidylprolyl isomerase (rotamase) activity catalyzed by FKBP12 with inhibition constants (K sub(i,app)) as low as 1 nM, yet they possess remarkable structural simplicity relative to FK506 and rapamycin, from which they are conceptually derived. The atomic structures of three FKBP12-ligand complexes and of one unbound ligand were determined by X-ray crystallography and are compared to the FKBP12-FK506 and FKBP12-rapamycin complexes.</description><identifier>ISSN: 0002-7863</identifier><identifier>EISSN: 1520-5126</identifier><identifier>DOI: 10.1021/ja00075a008</identifier><identifier>CODEN: JACSAT</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Biological and medical sciences ; Immunomodulators ; Medical sciences ; Pharmacology. Drug treatments</subject><ispartof>Journal of the American Chemical Society, 1993-11, Vol.115 (22), p.9925-9938</ispartof><rights>1994 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a361t-2cfae90092036ca2cbf3274572a0954680ce4ee34661c553ecddaf87e436767d3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/ja00075a008$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/ja00075a008$$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=3872789$$DView record in Pascal Francis$$Hfree_for_read</backlink></links><search><creatorcontrib>Holt, Dennis A</creatorcontrib><creatorcontrib>Luengo, Juan I</creatorcontrib><creatorcontrib>Yamashita, Dennis S</creatorcontrib><creatorcontrib>Oh, Hye Ja</creatorcontrib><creatorcontrib>Konialian, Arda L</creatorcontrib><creatorcontrib>Yen, Hwa Kwo</creatorcontrib><creatorcontrib>Rozamus, Leonard W</creatorcontrib><creatorcontrib>Brandt, Martin</creatorcontrib><creatorcontrib>Bossard, Mary J</creatorcontrib><title>Design, synthesis, and kinetic evaluation of high-affinity FKBP ligands and the X-ray crystal structures of their complexes with FKBP12</title><title>Journal of the American Chemical Society</title><addtitle>J. Am. Chem. Soc</addtitle><description>The design and synthesis of high-affinity FKBP12 ligands is described. These compounds potently inhibit the cis-trans-peptidylprolyl isomerase (rotamase) activity catalyzed by FKBP12 with inhibition constants (K sub(i,app)) as low as 1 nM, yet they possess remarkable structural simplicity relative to FK506 and rapamycin, from which they are conceptually derived. The atomic structures of three FKBP12-ligand complexes and of one unbound ligand were determined by X-ray crystallography and are compared to the FKBP12-FK506 and FKBP12-rapamycin complexes.</description><subject>Biological and medical sciences</subject><subject>Immunomodulators</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><issn>0002-7863</issn><issn>1520-5126</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><recordid>eNptkE1uFDEQhS0EEkNgxQW8QLAgDf5p291LEgigRCKCILGzCo8940mPe-JyQ_oEXBsnE0Us2Ljsqu89lx4hzzl7w5ngbzfAGDOqnt0DsuBKsEZxoR-SRe2LxnRaPiZPEDf12YqOL8if9x7jKh1SnFNZ1zseUkhLehmTL9FR_wuGCUocEx0DXcfVuoEQYoplpienR-d0iKvK462oGtAfTYaZujxjgYFiyZMrU_Z4I6_zmKkbt7vBX9fW71jWty5cPCWPAgzon93VA_L95MPF8afm7MvHz8fvzhqQmpdGuAC-Z6wXTGoHwv0MUphWGQGsV63umPOt97LVmjulpHfLJYTO-FZqo81SHpCXe99dHq8mj8VuIzo_DJD8OKHlWou-16aCr_egyyNi9sHuctxCni1n9iZs-0_YlX5xZwvoYAgZkot4L5GdEabrK9bssYjFX9-PIV_a-qVR9uL8mz3tvvZCKmOPKv9qz4NDuxmnnGo2_13gLxXCmjE</recordid><startdate>19931101</startdate><enddate>19931101</enddate><creator>Holt, Dennis A</creator><creator>Luengo, Juan I</creator><creator>Yamashita, Dennis S</creator><creator>Oh, Hye Ja</creator><creator>Konialian, Arda L</creator><creator>Yen, Hwa Kwo</creator><creator>Rozamus, Leonard W</creator><creator>Brandt, Martin</creator><creator>Bossard, Mary J</creator><general>American Chemical Society</general><scope>BSCLL</scope><scope>IQODW</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>19931101</creationdate><title>Design, synthesis, and kinetic evaluation of high-affinity FKBP ligands and the X-ray crystal structures of their complexes with FKBP12</title><author>Holt, Dennis A ; Luengo, Juan I ; Yamashita, Dennis S ; Oh, Hye Ja ; Konialian, Arda L ; Yen, Hwa Kwo ; Rozamus, Leonard W ; Brandt, Martin ; Bossard, Mary J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a361t-2cfae90092036ca2cbf3274572a0954680ce4ee34661c553ecddaf87e436767d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1993</creationdate><topic>Biological and medical sciences</topic><topic>Immunomodulators</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Holt, Dennis A</creatorcontrib><creatorcontrib>Luengo, Juan I</creatorcontrib><creatorcontrib>Yamashita, Dennis S</creatorcontrib><creatorcontrib>Oh, Hye Ja</creatorcontrib><creatorcontrib>Konialian, Arda L</creatorcontrib><creatorcontrib>Yen, Hwa Kwo</creatorcontrib><creatorcontrib>Rozamus, Leonard W</creatorcontrib><creatorcontrib>Brandt, Martin</creatorcontrib><creatorcontrib>Bossard, Mary J</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Journal of the American Chemical Society</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Holt, Dennis A</au><au>Luengo, Juan I</au><au>Yamashita, Dennis S</au><au>Oh, Hye Ja</au><au>Konialian, Arda L</au><au>Yen, Hwa Kwo</au><au>Rozamus, Leonard W</au><au>Brandt, Martin</au><au>Bossard, Mary J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Design, synthesis, and kinetic evaluation of high-affinity FKBP ligands and the X-ray crystal structures of their complexes with FKBP12</atitle><jtitle>Journal of the American Chemical Society</jtitle><addtitle>J. Am. Chem. Soc</addtitle><date>1993-11-01</date><risdate>1993</risdate><volume>115</volume><issue>22</issue><spage>9925</spage><epage>9938</epage><pages>9925-9938</pages><issn>0002-7863</issn><eissn>1520-5126</eissn><coden>JACSAT</coden><abstract>The design and synthesis of high-affinity FKBP12 ligands is described. These compounds potently inhibit the cis-trans-peptidylprolyl isomerase (rotamase) activity catalyzed by FKBP12 with inhibition constants (K sub(i,app)) as low as 1 nM, yet they possess remarkable structural simplicity relative to FK506 and rapamycin, from which they are conceptually derived. The atomic structures of three FKBP12-ligand complexes and of one unbound ligand were determined by X-ray crystallography and are compared to the FKBP12-FK506 and FKBP12-rapamycin complexes.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><doi>10.1021/ja00075a008</doi><tpages>14</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0002-7863 |
| ispartof | Journal of the American Chemical Society, 1993-11, Vol.115 (22), p.9925-9938 |
| issn | 0002-7863 1520-5126 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_16629967 |
| source | ACS Publications |
| subjects | Biological and medical sciences Immunomodulators Medical sciences Pharmacology. Drug treatments |
| title | Design, synthesis, and kinetic evaluation of high-affinity FKBP ligands and the X-ray crystal structures of their complexes with FKBP12 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T08%3A00%3A29IST&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=Design,%20synthesis,%20and%20kinetic%20evaluation%20of%20high-affinity%20FKBP%20ligands%20and%20the%20X-ray%20crystal%20structures%20of%20their%20complexes%20with%20FKBP12&rft.jtitle=Journal%20of%20the%20American%20Chemical%20Society&rft.au=Holt,%20Dennis%20A&rft.date=1993-11-01&rft.volume=115&rft.issue=22&rft.spage=9925&rft.epage=9938&rft.pages=9925-9938&rft.issn=0002-7863&rft.eissn=1520-5126&rft.coden=JACSAT&rft_id=info:doi/10.1021/ja00075a008&rft_dat=%3Cproquest_cross%3E16629967%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=16629967&rft_id=info:pmid/&rfr_iscdi=true |