Development of peptidyl α-keto-β-aldehydes as new inhibitors of cathepsin L — comparisons of potency and selectivity profiles with cathepsin B
We have utilized previously known substrate and inhibitor specificity profiles for the lysosomal cysteine protease, cathepsin L, to design a new series of putative inhibitors of this enzyme, based on di- and tri-peptidyl α-keto-β-aldehydes. Kinetic evaluation of these compounds revealed Z-Phe-Tyr(OB...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2000-08, Vol.10 (15), p.1771-1773 |
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| container_end_page | 1773 |
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| container_issue | 15 |
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| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 10 |
| creator | Lynas, John F Hawthorne, Susan J Walker, Brian |
| description | We have utilized previously known substrate and inhibitor specificity profiles for the lysosomal cysteine protease, cathepsin L, to design a new series of putative inhibitors of this enzyme, based on di- and tri-peptidyl α-keto-β-aldehydes. Kinetic evaluation of these compounds revealed Z-Phe-Tyr(OBut)-COCHO, with a
K
i=0.6 nM, to be the most potent, synthetic reversible inhibitor of cathepsin L reported to date. |
| doi_str_mv | 10.1016/S0960-894X(00)00340-1 |
| format | Article |
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K
i=0.6 nM, to be the most potent, synthetic reversible inhibitor of cathepsin L reported to date.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/S0960-894X(00)00340-1</identifier><identifier>PMID: 10937745</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Aldehydes - chemistry ; Biological and medical sciences ; Bones, joints and connective tissue. Antiinflammatory agents ; Cathepsin B - antagonists & inhibitors ; Cathepsin B - metabolism ; Cathepsin L ; Cathepsins - antagonists & inhibitors ; Cathepsins - metabolism ; Cysteine Endopeptidases ; Cysteine Proteinase Inhibitors - chemistry ; Cysteine Proteinase Inhibitors - metabolism ; Cysteine Proteinase Inhibitors - pharmacology ; Endopeptidases ; Humans ; Medical sciences ; Peptides - chemistry ; Pharmacology. Drug treatments ; Recombinant Proteins - antagonists & inhibitors ; Recombinant Proteins - metabolism ; Substrate Specificity</subject><ispartof>Bioorganic & medicinal chemistry letters, 2000-08, Vol.10 (15), p.1771-1773</ispartof><rights>2000 Elsevier Science Ltd</rights><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-74f8c78fb1b76c7fdf8321f39b5cdc81b13301ebd4f9b87c93f301cbb60e783b3</citedby><cites>FETCH-LOGICAL-c390t-74f8c78fb1b76c7fdf8321f39b5cdc81b13301ebd4f9b87c93f301cbb60e783b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960894X00003401$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1434632$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10937745$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lynas, John F</creatorcontrib><creatorcontrib>Hawthorne, Susan J</creatorcontrib><creatorcontrib>Walker, Brian</creatorcontrib><title>Development of peptidyl α-keto-β-aldehydes as new inhibitors of cathepsin L — comparisons of potency and selectivity profiles with cathepsin B</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>We have utilized previously known substrate and inhibitor specificity profiles for the lysosomal cysteine protease, cathepsin L, to design a new series of putative inhibitors of this enzyme, based on di- and tri-peptidyl α-keto-β-aldehydes. Kinetic evaluation of these compounds revealed Z-Phe-Tyr(OBut)-COCHO, with a
K
i=0.6 nM, to be the most potent, synthetic reversible inhibitor of cathepsin L reported to date.</description><subject>Aldehydes - chemistry</subject><subject>Biological and medical sciences</subject><subject>Bones, joints and connective tissue. Antiinflammatory agents</subject><subject>Cathepsin B - antagonists & inhibitors</subject><subject>Cathepsin B - metabolism</subject><subject>Cathepsin L</subject><subject>Cathepsins - antagonists & inhibitors</subject><subject>Cathepsins - metabolism</subject><subject>Cysteine Endopeptidases</subject><subject>Cysteine Proteinase Inhibitors - chemistry</subject><subject>Cysteine Proteinase Inhibitors - metabolism</subject><subject>Cysteine Proteinase Inhibitors - pharmacology</subject><subject>Endopeptidases</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Peptides - chemistry</subject><subject>Pharmacology. Drug treatments</subject><subject>Recombinant Proteins - antagonists & inhibitors</subject><subject>Recombinant Proteins - metabolism</subject><subject>Substrate Specificity</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU2O1DAQhSMEYpqBI4C8QAgWgfLYHScrBMOv1BILQGJn-aesNiRxsN09yo4zIC4CB5lDcBLcP4LZsbJK_t6r0ntVdZfCYwq0efIeugbqtuOfHgI8AmAcanqtWlDe8LoMy-vV4i9yUt1K6TMA5cD5zeqEQseE4MtF9f0FbrEP04BjJsGRCafs7dyTy5_1F8yhvvxVq97ieraYiEpkxAvix7XXPoeYdhKj8hqn5EeyIr-__SAmDJOKPoVx_z2FjKOZiRotSdijyX7r80ymGJzvi-mFz-srJs9vVzec6hPeOb6n1cdXLz-cv6lX716_PX-2qg3rINeCu9aI1mmqRWOEs65lZ9SxTi-NNS3VlDGgqC13nW6F6Zgrs9G6ARQt0-y0enDwLZd83WDKcvDJYN-rEcMmSUEFA9Z2BVweQBNDShGdnKIfVJwlBbkrQ-7LkLukJYDclyFp0d07LtjoAe0V1SH9Atw_AioZ1buoRuPTP44z3rCzgj09YFjS2HqMMhlfMkXrY4lT2uD_c8kfa4CsAg</recordid><startdate>20000807</startdate><enddate>20000807</enddate><creator>Lynas, John F</creator><creator>Hawthorne, Susan J</creator><creator>Walker, Brian</creator><general>Elsevier Ltd</general><general>Elsevier</general><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>20000807</creationdate><title>Development of peptidyl α-keto-β-aldehydes as new inhibitors of cathepsin L — comparisons of potency and selectivity profiles with cathepsin B</title><author>Lynas, John F ; Hawthorne, Susan J ; Walker, Brian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-74f8c78fb1b76c7fdf8321f39b5cdc81b13301ebd4f9b87c93f301cbb60e783b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Aldehydes - chemistry</topic><topic>Biological and medical sciences</topic><topic>Bones, joints and connective tissue. Antiinflammatory agents</topic><topic>Cathepsin B - antagonists & inhibitors</topic><topic>Cathepsin B - metabolism</topic><topic>Cathepsin L</topic><topic>Cathepsins - antagonists & inhibitors</topic><topic>Cathepsins - metabolism</topic><topic>Cysteine Endopeptidases</topic><topic>Cysteine Proteinase Inhibitors - chemistry</topic><topic>Cysteine Proteinase Inhibitors - metabolism</topic><topic>Cysteine Proteinase Inhibitors - pharmacology</topic><topic>Endopeptidases</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Peptides - chemistry</topic><topic>Pharmacology. Drug treatments</topic><topic>Recombinant Proteins - antagonists & inhibitors</topic><topic>Recombinant Proteins - metabolism</topic><topic>Substrate Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lynas, John F</creatorcontrib><creatorcontrib>Hawthorne, Susan J</creatorcontrib><creatorcontrib>Walker, Brian</creatorcontrib><collection>Pascal-Francis</collection><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>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lynas, John F</au><au>Hawthorne, Susan J</au><au>Walker, Brian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Development of peptidyl α-keto-β-aldehydes as new inhibitors of cathepsin L — comparisons of potency and selectivity profiles with cathepsin B</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2000-08-07</date><risdate>2000</risdate><volume>10</volume><issue>15</issue><spage>1771</spage><epage>1773</epage><pages>1771-1773</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>We have utilized previously known substrate and inhibitor specificity profiles for the lysosomal cysteine protease, cathepsin L, to design a new series of putative inhibitors of this enzyme, based on di- and tri-peptidyl α-keto-β-aldehydes. 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K
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| fulltext | fulltext |
| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2000-08, Vol.10 (15), p.1771-1773 |
| issn | 0960-894X 1464-3405 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Aldehydes - chemistry Biological and medical sciences Bones, joints and connective tissue. Antiinflammatory agents Cathepsin B - antagonists & inhibitors Cathepsin B - metabolism Cathepsin L Cathepsins - antagonists & inhibitors Cathepsins - metabolism Cysteine Endopeptidases Cysteine Proteinase Inhibitors - chemistry Cysteine Proteinase Inhibitors - metabolism Cysteine Proteinase Inhibitors - pharmacology Endopeptidases Humans Medical sciences Peptides - chemistry Pharmacology. Drug treatments Recombinant Proteins - antagonists & inhibitors Recombinant Proteins - metabolism Substrate Specificity |
| title | Development of peptidyl α-keto-β-aldehydes as new inhibitors of cathepsin L — comparisons of potency and selectivity profiles with cathepsin B |
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