Linked Life Data

3950912

Source:http://linkedlifedata.com/resource/pubmed/id/3950912

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1986-3-31
pubmed:abstractText
Monosubstituted adenosine 5'-triphosphate (ATP) derivatives with a substituent of up to four atoms at any of eight positions in the adenosine moiety, or with an isosteric group replacement at O5' or in the triphosphate moiety, have been evaluated kinetically as substrates and inhibitors of liver (I), kidney (II), and Novikoff hepatoma (T) variants of rat methionine adenosyltransferase. Inhibitory potencies were expressed as KM(ATP)/Ki (for competitive inhibition vs. ATP) or as KM(ATP)/KM when no Ki value was available. Variant I was inhibited more powerfully than II or T by all of four ATP derivatives for which comparative data were obtained. Among 15 ATP derivatives, four were substrates of II or T and the remainder inhibited II and T competitively with respect to ATP; most derivatives exhibited at least moderate (greater than 0.5) inhibitory potency. Differential inhibition of II and T was shown by 11 of 14 ATP derivatives; relative inhibitory potencies (T:II) ranged from 5.5 with 2-SCH3-ATP [KM(ATP)/Ki = 1.3 with T] to 0.24 with the ATP isostere with a C5'-CH2-P alpha system [KM(ATP)/Ki = 1.9 with II]. The most effective inhibitor was the P beta, P gamma imido isostere of ATP with inhibitory potencies of 25 and 35 for II and T, respectively. The findings provide further evidence that substrate derivatives with single short groups attached at various positions, or with single isosteric group replacements, are frequently useful probes in the design of isozyme-selective inhibitors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
318-22
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1986
pubmed:articleTitle
Isozyme-specific enzyme inhibitors. 10. Adenosine 5'-triphosphate derivatives as substrates or inhibitors of methionine adenosyltransferases of rat normal and hepatoma tissues.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't