The synthesis of ketomethylene pseudopeptide analogues of dipeptide aldehyde inhibitors of calpain
The ketomethylene phenylalanal and alanal analogues of Cbz-Val-Phe-H and Cbz-Val-Ala-H have been prepared and the K i values versus chicken gizzard smooth muscle calpain were determined. The ketomethylene isosteres were significantly less potent than the corresponding dipeptide aldehydes, and this l...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 1999-01, Vol.9 (2), p.139-140 |
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| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 9 |
| creator | Angelastro, Michael R. Marquart, Angela L. Mehdi, Shujaath Koehl, Jack R. Vaz, Roy J. Bey, Philippe Peet, Norton P. |
| description | The ketomethylene phenylalanal and alanal analogues of Cbz-Val-Phe-H and Cbz-Val-Ala-H have been prepared and the K
i values versus chicken gizzard smooth muscle calpain were determined. The ketomethylene isosteres were significantly less potent than the corresponding dipeptide aldehydes, and this loss in activity is attributed to the absence of a critical interaction between the P1–P2 amide bond and the peptide binding region of calpain.
The ketomethylene phenylalanal and alanal analogues of Cbz-Val-Phe-H and Cbz-Val-Ala-H have been prepared from α-methylene-γ-butyrolactone
4. The subsequent arylation, reduction, and bis-Swern oxidation generated the targeted γ-ketoaldehyde
9. |
| doi_str_mv | 10.1016/S0960-894X(98)00704-5 |
| format | Article |
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i values versus chicken gizzard smooth muscle calpain were determined. The ketomethylene isosteres were significantly less potent than the corresponding dipeptide aldehydes, and this loss in activity is attributed to the absence of a critical interaction between the P1–P2 amide bond and the peptide binding region of calpain.
The ketomethylene phenylalanal and alanal analogues of Cbz-Val-Phe-H and Cbz-Val-Ala-H have been prepared from α-methylene-γ-butyrolactone
4. The subsequent arylation, reduction, and bis-Swern oxidation generated the targeted γ-ketoaldehyde
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i values versus chicken gizzard smooth muscle calpain were determined. The ketomethylene isosteres were significantly less potent than the corresponding dipeptide aldehydes, and this loss in activity is attributed to the absence of a critical interaction between the P1–P2 amide bond and the peptide binding region of calpain.
The ketomethylene phenylalanal and alanal analogues of Cbz-Val-Phe-H and Cbz-Val-Ala-H have been prepared from α-methylene-γ-butyrolactone
4. The subsequent arylation, reduction, and bis-Swern oxidation generated the targeted γ-ketoaldehyde
9.</description><subject>Aldehydes - chemistry</subject><subject>Aliphatic compounds</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Calpain - antagonists & inhibitors</subject><subject>Calpain - chemistry</subject><subject>Chemistry</subject><subject>Chickens</subject><subject>Exact sciences and technology</subject><subject>Gizzard, Avian - chemistry</subject><subject>Ketones - chemistry</subject><subject>Medical sciences</subject><subject>Muscle, Smooth - chemistry</subject><subject>Neuropharmacology</subject><subject>Neuroprotective agent</subject><subject>Organic chemistry</subject><subject>Peptide Fragments - chemistry</subject><subject>Pharmacology. Drug treatments</subject><subject>Preparations and properties</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtP3DAURq0KVAban1CUBapgkfb6kYdXqEK8JCQWpVJ3lmNfE7eZOLUzSPPvMTMjyo7Vta7OZ38-hHyh8I0Crb__BFlD2Urx-1S2ZwANiLL6QBZU1KLkAqo9snhFDshhSn8AqAAhPpIDCsCopNWCdA89Fmk9zj0mn4rgir84hyXO_XrAEYsp4cqGCafZWyz0qIfwuMINaP3rerDYr_PBj73v_BziBjB6mLQfP5F9p4eEn3fziPy6uny4uCnv7q9vL37clYZLmEtneNt2HTjbSGGNbZxDx6VhUNfMtQgcOWuYpJZRpILaruHQScds3dKaGn5Evm7vnWL4lzvOaumTwWHQI4ZVUrWsWhBMZrDagiaGlCI6NUW_1HGtKKgXuWojV72YU7JVG7mqyrnj3QOrbon2TWprMwMnO0Cn_HkX9Wh8-s_lopyyjJ1vMcw2njxGlYzH0aD1Ec2sbPDvNHkGllqYfA</recordid><startdate>19990118</startdate><enddate>19990118</enddate><creator>Angelastro, Michael R.</creator><creator>Marquart, Angela L.</creator><creator>Mehdi, Shujaath</creator><creator>Koehl, Jack R.</creator><creator>Vaz, Roy J.</creator><creator>Bey, Philippe</creator><creator>Peet, Norton P.</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>19990118</creationdate><title>The synthesis of ketomethylene pseudopeptide analogues of dipeptide aldehyde inhibitors of calpain</title><author>Angelastro, Michael R. ; Marquart, Angela L. ; Mehdi, Shujaath ; Koehl, Jack R. ; Vaz, Roy J. ; Bey, Philippe ; Peet, Norton P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-fc388bb0fd794dcd7ffef39c20662f8e03e327291d21e141db730b9f2d68161c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Aldehydes - chemistry</topic><topic>Aliphatic compounds</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Calpain - antagonists & inhibitors</topic><topic>Calpain - chemistry</topic><topic>Chemistry</topic><topic>Chickens</topic><topic>Exact sciences and technology</topic><topic>Gizzard, Avian - chemistry</topic><topic>Ketones - chemistry</topic><topic>Medical sciences</topic><topic>Muscle, Smooth - chemistry</topic><topic>Neuropharmacology</topic><topic>Neuroprotective agent</topic><topic>Organic chemistry</topic><topic>Peptide Fragments - chemistry</topic><topic>Pharmacology. Drug treatments</topic><topic>Preparations and properties</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Angelastro, Michael R.</creatorcontrib><creatorcontrib>Marquart, Angela L.</creatorcontrib><creatorcontrib>Mehdi, Shujaath</creatorcontrib><creatorcontrib>Koehl, Jack R.</creatorcontrib><creatorcontrib>Vaz, Roy J.</creatorcontrib><creatorcontrib>Bey, Philippe</creatorcontrib><creatorcontrib>Peet, Norton P.</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>Angelastro, Michael R.</au><au>Marquart, Angela L.</au><au>Mehdi, Shujaath</au><au>Koehl, Jack R.</au><au>Vaz, Roy J.</au><au>Bey, Philippe</au><au>Peet, Norton P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The synthesis of ketomethylene pseudopeptide analogues of dipeptide aldehyde inhibitors of calpain</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>1999-01-18</date><risdate>1999</risdate><volume>9</volume><issue>2</issue><spage>139</spage><epage>140</epage><pages>139-140</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>The ketomethylene phenylalanal and alanal analogues of Cbz-Val-Phe-H and Cbz-Val-Ala-H have been prepared and the K
i values versus chicken gizzard smooth muscle calpain were determined. The ketomethylene isosteres were significantly less potent than the corresponding dipeptide aldehydes, and this loss in activity is attributed to the absence of a critical interaction between the P1–P2 amide bond and the peptide binding region of calpain.
The ketomethylene phenylalanal and alanal analogues of Cbz-Val-Phe-H and Cbz-Val-Ala-H have been prepared from α-methylene-γ-butyrolactone
4. The subsequent arylation, reduction, and bis-Swern oxidation generated the targeted γ-ketoaldehyde
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| fulltext | fulltext |
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| ispartof | Bioorganic & medicinal chemistry letters, 1999-01, Vol.9 (2), p.139-140 |
| issn | 0960-894X 1464-3405 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Aldehydes - chemistry Aliphatic compounds Animals Biological and medical sciences Calpain - antagonists & inhibitors Calpain - chemistry Chemistry Chickens Exact sciences and technology Gizzard, Avian - chemistry Ketones - chemistry Medical sciences Muscle, Smooth - chemistry Neuropharmacology Neuroprotective agent Organic chemistry Peptide Fragments - chemistry Pharmacology. Drug treatments Preparations and properties |
| title | The synthesis of ketomethylene pseudopeptide analogues of dipeptide aldehyde inhibitors of calpain |
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