Molecular Modeling, Synthesis, and Biological Evaluation of Macrocyclic Calpain Inhibitors
The design and elaboration of a series of macrocyclic templates that exhibit a propensity to adopt a β-strand-like peptide-backbone conformation led to potent and selective inhibitors of calpain 2. Macrocycle 1 retarded calcium-induced opacification in an ovine-lens culture assay and is a lead compo...
Gespeichert in:
| Veröffentlicht in: | Angewandte Chemie (International ed.) 2009-01, Vol.48 (8), p.1455-1458 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1458 |
|---|---|
| container_issue | 8 |
| container_start_page | 1455 |
| container_title | Angewandte Chemie (International ed.) |
| container_volume | 48 |
| creator | Abell, Andrew D Jones, Matthew A Coxon, James M Morton, James D Aitken, Steven G McNabb, Stephen B Lee, Hannah Y.-Y Mehrtens, Janna M Alexander, Nathan A Stuart, Blair G Neffe, Axel T Bickerstaffe, Roy |
| description | The design and elaboration of a series of macrocyclic templates that exhibit a propensity to adopt a β-strand-like peptide-backbone conformation led to potent and selective inhibitors of calpain 2. Macrocycle 1 retarded calcium-induced opacification in an ovine-lens culture assay and is a lead compound for the development of a drug for cataract treatment. Cbz=carbobenzyloxy. |
| doi_str_mv | 10.1002/anie.200805014 |
| format | Article |
| fullrecord | <record><control><sourceid>wiley_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1002_anie_200805014</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>ANIE200805014</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4334-8d14e2cee8ae52b6a5e9859a9df6d0e453b79fd4d4cc6508b22cc8199babc45e3</originalsourceid><addsrcrecordid>eNqFkEFPwjAYhhujEUWvHrU_gGHbtVt7RIJKAnpALl6Wb10HNWUlK2j27x0ZUW-evu_wvG_ePAjdUDKkhLB7qKwZMkIkEYTyE3RBBaNRnKbxafvzOI5SKWgPXYbw0fJSkuQc9aiiXCSUXaD3uXdG7x3UeO4L42y1GuBFU-3WJtgwwFAV-MF651dWg8OTT3B72FlfYV_iOeja60Y7q_EY3BZshafV2uZ25-twhc5KcMFcH28fLR8nb-PnaPb6NB2PZpFu5_FIFpQbpo2RYATLExBGSaFAFWVSEMNFnKeqLHjBtU4EkTljWkuqVA655sLEfTTsetsxIdSmzLa13UDdZJRkB0nZQVL2I6kN3HaB7T7fmOIXP1ppAdUBX9aZ5p-6bPQynfwtv-uyJfgMVrUN2XLBCI0JFYpTlcbfmhh-EA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Molecular Modeling, Synthesis, and Biological Evaluation of Macrocyclic Calpain Inhibitors</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Abell, Andrew D ; Jones, Matthew A ; Coxon, James M ; Morton, James D ; Aitken, Steven G ; McNabb, Stephen B ; Lee, Hannah Y.-Y ; Mehrtens, Janna M ; Alexander, Nathan A ; Stuart, Blair G ; Neffe, Axel T ; Bickerstaffe, Roy</creator><creatorcontrib>Abell, Andrew D ; Jones, Matthew A ; Coxon, James M ; Morton, James D ; Aitken, Steven G ; McNabb, Stephen B ; Lee, Hannah Y.-Y ; Mehrtens, Janna M ; Alexander, Nathan A ; Stuart, Blair G ; Neffe, Axel T ; Bickerstaffe, Roy</creatorcontrib><description>The design and elaboration of a series of macrocyclic templates that exhibit a propensity to adopt a β-strand-like peptide-backbone conformation led to potent and selective inhibitors of calpain 2. Macrocycle 1 retarded calcium-induced opacification in an ovine-lens culture assay and is a lead compound for the development of a drug for cataract treatment. Cbz=carbobenzyloxy.</description><identifier>ISSN: 1433-7851</identifier><identifier>EISSN: 1521-3773</identifier><identifier>DOI: 10.1002/anie.200805014</identifier><identifier>PMID: 19145612</identifier><language>eng</language><publisher>Weinheim: Wiley-VCH Verlag</publisher><subject>Animals ; biological activity ; Calpain - antagonists & inhibitors ; Calpain - metabolism ; Cataract - chemically induced ; Cataract - drug therapy ; Cysteine Proteinase Inhibitors - chemical synthesis ; Cysteine Proteinase Inhibitors - chemistry ; Cysteine Proteinase Inhibitors - pharmacology ; Heterocyclic Compounds - chemical synthesis ; Heterocyclic Compounds - chemistry ; inhibitors ; Inhibitory Concentration 50 ; Lens, Crystalline - metabolism ; macrocycles ; Macrocyclic Compounds - chemical synthesis ; Macrocyclic Compounds - chemistry ; Macrocyclic Compounds - pharmacology ; Models, Molecular ; molecular modeling ; peptides ; Sheep ; Structure-Activity Relationship</subject><ispartof>Angewandte Chemie (International ed.), 2009-01, Vol.48 (8), p.1455-1458</ispartof><rights>Copyright © 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4334-8d14e2cee8ae52b6a5e9859a9df6d0e453b79fd4d4cc6508b22cc8199babc45e3</citedby><cites>FETCH-LOGICAL-c4334-8d14e2cee8ae52b6a5e9859a9df6d0e453b79fd4d4cc6508b22cc8199babc45e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fanie.200805014$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fanie.200805014$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19145612$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Abell, Andrew D</creatorcontrib><creatorcontrib>Jones, Matthew A</creatorcontrib><creatorcontrib>Coxon, James M</creatorcontrib><creatorcontrib>Morton, James D</creatorcontrib><creatorcontrib>Aitken, Steven G</creatorcontrib><creatorcontrib>McNabb, Stephen B</creatorcontrib><creatorcontrib>Lee, Hannah Y.-Y</creatorcontrib><creatorcontrib>Mehrtens, Janna M</creatorcontrib><creatorcontrib>Alexander, Nathan A</creatorcontrib><creatorcontrib>Stuart, Blair G</creatorcontrib><creatorcontrib>Neffe, Axel T</creatorcontrib><creatorcontrib>Bickerstaffe, Roy</creatorcontrib><title>Molecular Modeling, Synthesis, and Biological Evaluation of Macrocyclic Calpain Inhibitors</title><title>Angewandte Chemie (International ed.)</title><addtitle>Angew Chem Int Ed Engl</addtitle><description>The design and elaboration of a series of macrocyclic templates that exhibit a propensity to adopt a β-strand-like peptide-backbone conformation led to potent and selective inhibitors of calpain 2. Macrocycle 1 retarded calcium-induced opacification in an ovine-lens culture assay and is a lead compound for the development of a drug for cataract treatment. Cbz=carbobenzyloxy.</description><subject>Animals</subject><subject>biological activity</subject><subject>Calpain - antagonists & inhibitors</subject><subject>Calpain - metabolism</subject><subject>Cataract - chemically induced</subject><subject>Cataract - drug therapy</subject><subject>Cysteine Proteinase Inhibitors - chemical synthesis</subject><subject>Cysteine Proteinase Inhibitors - chemistry</subject><subject>Cysteine Proteinase Inhibitors - pharmacology</subject><subject>Heterocyclic Compounds - chemical synthesis</subject><subject>Heterocyclic Compounds - chemistry</subject><subject>inhibitors</subject><subject>Inhibitory Concentration 50</subject><subject>Lens, Crystalline - metabolism</subject><subject>macrocycles</subject><subject>Macrocyclic Compounds - chemical synthesis</subject><subject>Macrocyclic Compounds - chemistry</subject><subject>Macrocyclic Compounds - pharmacology</subject><subject>Models, Molecular</subject><subject>molecular modeling</subject><subject>peptides</subject><subject>Sheep</subject><subject>Structure-Activity Relationship</subject><issn>1433-7851</issn><issn>1521-3773</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEFPwjAYhhujEUWvHrU_gGHbtVt7RIJKAnpALl6Wb10HNWUlK2j27x0ZUW-evu_wvG_ePAjdUDKkhLB7qKwZMkIkEYTyE3RBBaNRnKbxafvzOI5SKWgPXYbw0fJSkuQc9aiiXCSUXaD3uXdG7x3UeO4L42y1GuBFU-3WJtgwwFAV-MF651dWg8OTT3B72FlfYV_iOeja60Y7q_EY3BZshafV2uZ25-twhc5KcMFcH28fLR8nb-PnaPb6NB2PZpFu5_FIFpQbpo2RYATLExBGSaFAFWVSEMNFnKeqLHjBtU4EkTljWkuqVA655sLEfTTsetsxIdSmzLa13UDdZJRkB0nZQVL2I6kN3HaB7T7fmOIXP1ppAdUBX9aZ5p-6bPQynfwtv-uyJfgMVrUN2XLBCI0JFYpTlcbfmhh-EA</recordid><startdate>20090101</startdate><enddate>20090101</enddate><creator>Abell, Andrew D</creator><creator>Jones, Matthew A</creator><creator>Coxon, James M</creator><creator>Morton, James D</creator><creator>Aitken, Steven G</creator><creator>McNabb, Stephen B</creator><creator>Lee, Hannah Y.-Y</creator><creator>Mehrtens, Janna M</creator><creator>Alexander, Nathan A</creator><creator>Stuart, Blair G</creator><creator>Neffe, Axel T</creator><creator>Bickerstaffe, Roy</creator><general>Wiley-VCH Verlag</general><general>WILEY‐VCH Verlag</general><scope>FBQ</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></search><sort><creationdate>20090101</creationdate><title>Molecular Modeling, Synthesis, and Biological Evaluation of Macrocyclic Calpain Inhibitors</title><author>Abell, Andrew D ; Jones, Matthew A ; Coxon, James M ; Morton, James D ; Aitken, Steven G ; McNabb, Stephen B ; Lee, Hannah Y.-Y ; Mehrtens, Janna M ; Alexander, Nathan A ; Stuart, Blair G ; Neffe, Axel T ; Bickerstaffe, Roy</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4334-8d14e2cee8ae52b6a5e9859a9df6d0e453b79fd4d4cc6508b22cc8199babc45e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>biological activity</topic><topic>Calpain - antagonists & inhibitors</topic><topic>Calpain - metabolism</topic><topic>Cataract - chemically induced</topic><topic>Cataract - drug therapy</topic><topic>Cysteine Proteinase Inhibitors - chemical synthesis</topic><topic>Cysteine Proteinase Inhibitors - chemistry</topic><topic>Cysteine Proteinase Inhibitors - pharmacology</topic><topic>Heterocyclic Compounds - chemical synthesis</topic><topic>Heterocyclic Compounds - chemistry</topic><topic>inhibitors</topic><topic>Inhibitory Concentration 50</topic><topic>Lens, Crystalline - metabolism</topic><topic>macrocycles</topic><topic>Macrocyclic Compounds - chemical synthesis</topic><topic>Macrocyclic Compounds - chemistry</topic><topic>Macrocyclic Compounds - pharmacology</topic><topic>Models, Molecular</topic><topic>molecular modeling</topic><topic>peptides</topic><topic>Sheep</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Abell, Andrew D</creatorcontrib><creatorcontrib>Jones, Matthew A</creatorcontrib><creatorcontrib>Coxon, James M</creatorcontrib><creatorcontrib>Morton, James D</creatorcontrib><creatorcontrib>Aitken, Steven G</creatorcontrib><creatorcontrib>McNabb, Stephen B</creatorcontrib><creatorcontrib>Lee, Hannah Y.-Y</creatorcontrib><creatorcontrib>Mehrtens, Janna M</creatorcontrib><creatorcontrib>Alexander, Nathan A</creatorcontrib><creatorcontrib>Stuart, Blair G</creatorcontrib><creatorcontrib>Neffe, Axel T</creatorcontrib><creatorcontrib>Bickerstaffe, Roy</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Angewandte Chemie (International ed.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Abell, Andrew D</au><au>Jones, Matthew A</au><au>Coxon, James M</au><au>Morton, James D</au><au>Aitken, Steven G</au><au>McNabb, Stephen B</au><au>Lee, Hannah Y.-Y</au><au>Mehrtens, Janna M</au><au>Alexander, Nathan A</au><au>Stuart, Blair G</au><au>Neffe, Axel T</au><au>Bickerstaffe, Roy</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular Modeling, Synthesis, and Biological Evaluation of Macrocyclic Calpain Inhibitors</atitle><jtitle>Angewandte Chemie (International ed.)</jtitle><addtitle>Angew Chem Int Ed Engl</addtitle><date>2009-01-01</date><risdate>2009</risdate><volume>48</volume><issue>8</issue><spage>1455</spage><epage>1458</epage><pages>1455-1458</pages><issn>1433-7851</issn><eissn>1521-3773</eissn><abstract>The design and elaboration of a series of macrocyclic templates that exhibit a propensity to adopt a β-strand-like peptide-backbone conformation led to potent and selective inhibitors of calpain 2. Macrocycle 1 retarded calcium-induced opacification in an ovine-lens culture assay and is a lead compound for the development of a drug for cataract treatment. Cbz=carbobenzyloxy.</abstract><cop>Weinheim</cop><pub>Wiley-VCH Verlag</pub><pmid>19145612</pmid><doi>10.1002/anie.200805014</doi><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1433-7851 |
| ispartof | Angewandte Chemie (International ed.), 2009-01, Vol.48 (8), p.1455-1458 |
| issn | 1433-7851 1521-3773 |
| language | eng |
| recordid | cdi_crossref_primary_10_1002_anie_200805014 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Animals biological activity Calpain - antagonists & inhibitors Calpain - metabolism Cataract - chemically induced Cataract - drug therapy Cysteine Proteinase Inhibitors - chemical synthesis Cysteine Proteinase Inhibitors - chemistry Cysteine Proteinase Inhibitors - pharmacology Heterocyclic Compounds - chemical synthesis Heterocyclic Compounds - chemistry inhibitors Inhibitory Concentration 50 Lens, Crystalline - metabolism macrocycles Macrocyclic Compounds - chemical synthesis Macrocyclic Compounds - chemistry Macrocyclic Compounds - pharmacology Models, Molecular molecular modeling peptides Sheep Structure-Activity Relationship |
| title | Molecular Modeling, Synthesis, and Biological Evaluation of Macrocyclic Calpain Inhibitors |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T15%3A24%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-wiley_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Molecular%20Modeling,%20Synthesis,%20and%20Biological%20Evaluation%20of%20Macrocyclic%20Calpain%20Inhibitors&rft.jtitle=Angewandte%20Chemie%20(International%20ed.)&rft.au=Abell,%20Andrew%20D&rft.date=2009-01-01&rft.volume=48&rft.issue=8&rft.spage=1455&rft.epage=1458&rft.pages=1455-1458&rft.issn=1433-7851&rft.eissn=1521-3773&rft_id=info:doi/10.1002/anie.200805014&rft_dat=%3Cwiley_cross%3EANIE200805014%3C/wiley_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/19145612&rfr_iscdi=true |