Source:http://linkedlifedata.com/resource/pubmed/id/10938538
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2001-1-26
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pubmed:abstractText |
L-alanine hydroxamate derivatives were obtained by reaction of alkyl/arylsulfonyl halides with L-alanine, followed by treatment with benzyl chloride, and conversion of the COOH moiety to the CONHOH group with hydroxylamine in the presence of carbodiimides. Other derivatives were obtained by reaction of N-benzyl-alanine with aryl isocyanates, arylsulfonyl isocyanates or benzoyl isothiocyanate, followed by a similar conversion of the COOH to the CONHOH moiety. The obtained compounds were assayed as inhibitors of Clostridium histolyticum collagenase, ChC (EC 3.4.24.3), a zinc enzyme which degrades triple helical collagen. The hydroxamate derivatives were generally 100-500 times more active than the corresponding carboxylates. In the series of synthesized derivatives, substitution patterns leading to the most potent ChC inhibitors were those involving perfluoroalkylsulfonyl- and substituted-arylsulfonyl moieties, such as pentafluorophenylsulfonyl, 3- and 4-protected-aminophenylsulfonyl-, 3- and 4-carboxy-phenylsulfonyl-, 3-trifluoromethyl-phenylsulfonyl-, or 1- and 2-naphthylsulfonyl among others. Similarly to the matrix metalloproteinase (MMP) hydroxamate inhibitors, ChC inhibitors of the type reported here must incorporate hydrophobic moieties at the P(2') and P(3') sites, in order to achieve tight binding to the enzyme.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Alanine,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxamic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Microbial Collagenase,
http://linkedlifedata.com/resource/pubmed/chemical/Phenylalanine,
http://linkedlifedata.com/resource/pubmed/chemical/Protease Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Thiophenes,
http://linkedlifedata.com/resource/pubmed/chemical/batimastat
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pubmed:status |
MEDLINE
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pubmed:issn |
8755-5093
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
15
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
111-28
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:10938538-Alanine,
pubmed-meshheading:10938538-Clostridium,
pubmed-meshheading:10938538-Hydroxamic Acids,
pubmed-meshheading:10938538-Microbial Collagenase,
pubmed-meshheading:10938538-Phenylalanine,
pubmed-meshheading:10938538-Protease Inhibitors,
pubmed-meshheading:10938538-Thiophenes
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pubmed:year |
2000
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pubmed:articleTitle |
Protease inhibitors: Synthesis of L-alanine hydroxamate sulfonylated derivatives as inhibitors of clostridium histolyticum collagenase.
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pubmed:affiliation |
Università degli Studi, Laboratorio di Chimica Inorganica e Bioinorganica, Via Gino Capponi 7, I-50121, Florence, Italy. cts@bio.chim.unifi.it
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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