Linked Life Data

3257524

Source:http://linkedlifedata.com/resource/pubmed/id/3257524

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1988-3-16
pubmed:abstractText
With 2',3'-O-isopropylideneadenosine or its N6-benzoyl derivative as starting material, synthetic routes to two novel adducts of L-methionine and beta,gamma-imido-ATP have been devised. One adduct, 14 (2:3 mixture of 6' epimers), had a P alpha OCH(R1)CH2 system [R1 = CH2-L-SCH2CH2CH2CH(NH2)CO2H] in place of the P alpha OC(5')H2 system of ATP, while the other, 16 (2:3 mixture of 5' epimers), had a P alpha OCH2CH2CH(R2) system [R2 = L-SCH2CH2CH(NH2)CO2H]. The ribose-P alpha bridge in 14 and 16 contained one more methylene group than in two homologous methionine-ATP adducts studied previously. Adduct 14 was a potent inhibitor of the rat M-2 (normal tissue) and M-T (Novikoff ascitic hepatoma) variants of methionine adenosyltransferase and gave competitive kinetics vs MgATP (Ki = 0.39 and 0.63 microM, respectively) or vs L-methionine (Ki = 2.2 and 2.7 microM). Adduct 16 was likewise a potent inhibitor competitive vs MgATP (Ki = 0.44 and 0.81 microM, respectively) or L-methionine (Ki = 2.1 and 1.5 microM). The kinetic data indicate that 14 and 16 inhibit by binding simultaneously to the MgATP and L-methionine substrate sites and that the extra methylene group facilitates the interaction of their methionine residues with these methionine sites.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
384-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
Toward the synthesis of isozyme-specific enzyme inhibitors. Potent inhibitors of rat methionine adenosyltransferases. Effect of one-atom elongation of the ribose-P alpha bridge in two covalent adducts of L-methionine and beta,gamma-imido-ATP.
pubmed:affiliation
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't