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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
1989-5-15
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pubmed:abstractText |
N6,N6-Dibenzoyl-2',3'-O-isopropylideneadenosine, which is readily synthesized by one-pot 5'-O-trimethylsilylation, N6-benzoylation, and desilylation, was converted to the corresponding 5'-aldehyde. This was treated with CH2 = CHMgBr to afford, after debenzoylation, a 1:3 mixture of the 5'S and 5'R epimers, respectively, of 5'-C-vinyl-2',3'-O-isopropylideneadenosine. The configurations were established by single-crystal X-ray diffraction analysis of the 5'R epimer. Hydroboration of the 5'-O-tetrahydropyranyl derivative of the mixed epimeric 5'-C-vinyl nucleosides readily furnished 5'(S,R)-C-(2-hydroxyethyl)-2',3'-O-isopropylideneadenosine. Treatment of the 5'(S,R)-C-(2-O-tosyl) derivative of this with disodium L-homocysteinate permitted facile introduction of the L-ethionine system. By means of methods developed earlier in the synthesis of homologous methionine-ATP adducts, the alpha-amino acid group was protected, a beta,gamma-imidotriphosphoryl group was introduced at O5', and blocking groups were removed to give the title adduct as a 2:3 mixture of its two 5' epimers. It was a powerful inhibitor [KM(ATP)/Ki = 520 and 340] of the M-2 (normal tissue) and M-T (hepatoma tissue) forms, respectively, of the title enzyme and displayed predominantly competitive kinetics with the two substrates L-methionine and MgATP. It inhibited M-2 and M-T slightly less effectively than its homologue possessing one less CH2 between sulfur and C5' and gave kinetic evidence of an increased tendency to form L-methionine-enzyme-adduct and MgATP-enzyme-adduct complexes.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Adenylyl Imidodiphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Ethionine,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Methionine,
http://linkedlifedata.com/resource/pubmed/chemical/Methionine Adenosyltransferase,
http://linkedlifedata.com/resource/pubmed/chemical/Transferases
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0022-2623
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
32
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
885-90
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:2784835-Adenosine Triphosphate,
pubmed-meshheading:2784835-Adenylyl Imidodiphosphate,
pubmed-meshheading:2784835-Animals,
pubmed-meshheading:2784835-Binding, Competitive,
pubmed-meshheading:2784835-Chemical Phenomena,
pubmed-meshheading:2784835-Chemistry,
pubmed-meshheading:2784835-Chromatography, High Pressure Liquid,
pubmed-meshheading:2784835-Ethionine,
pubmed-meshheading:2784835-Isoenzymes,
pubmed-meshheading:2784835-Kinetics,
pubmed-meshheading:2784835-Magnetic Resonance Spectroscopy,
pubmed-meshheading:2784835-Methionine,
pubmed-meshheading:2784835-Methionine Adenosyltransferase,
pubmed-meshheading:2784835-Molecular Structure,
pubmed-meshheading:2784835-Rats,
pubmed-meshheading:2784835-Structure-Activity Relationship,
pubmed-meshheading:2784835-Transferases
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pubmed:year |
1989
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pubmed:articleTitle |
Approaches to isozyme-specific inhibitors. 16. A novel methyl-C5' covalent adduct of L-ethionine and beta,gamma-imido-ATP as a potent multisubstrate inhibitor of rat methionine adenosyltransferases.
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pubmed:affiliation |
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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