Linked Life Data

187750

Source:http://linkedlifedata.com/resource/pubmed/id/187750

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1977-2-24
pubmed:abstractText
Nineteen derivatives of adenosine 5'-phosphate (AMP) bearing acylaminomethyl, acetoxy, or alkylaminomethyl substituents on the phosphate-ribose bridge (5' and O-5' positions) of AMP together with 2',3'-O-ethylidene, 2',3',-O-isopropylidene, and 2',3'-di-O-acetyl derivatives of AMP have been synthesized. Their substrate and/or competitive inhibitor properties with pig rabbit muscle AMP kinases indicate that all the substituents except 2',3'-O-ethlidene with the pig enzyme permitted binding of AMP at its enzymic site. Determination of enzyme-inhibitor dissociation constants showed that several compounds with substituents on the ribose-phosphate bridge bind as well or better than AMP. The affinity is ascribed in part to interaction between substituents and a lipophilic region of the enzymes adjacent to the ribose-phosphate bridge in the enzyme-AMP complexes. The enzyme-inhibitor dissociation constants reveal a structural dissimilarity between the pig and rabbit enzymes in the vicinity of the lipophilic region. The substrate and inhibitor properties of eight ATP derivatives gave evidence that affinity of ATP for its substrate site on the AMP kinases is compatible with acetyl- or chloroacetylaminomethyl groups at the phosphate-ribose bridge or with 2',3'-O-ethylidene or isopropylidene residues. The yeast hexokinase-ATP complex tolerated an acetylaminomethyl group at C-5' or a benzoylaminomethyl group adjacent to O-5'. The present findings regarding substituent tolerance could be used in the design of adenine nucleotide site-directed irreversible inhibitors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1371-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1976
pubmed:articleTitle
Design of substrate-site-directed inhibitors of adenylate kinase and hexokinase. Effect of substrate substituents on affinity on affinity for the adenine nucleotide sites.
pubmed:publicationType
Journal Article, Comparative Study, In Vitro, Research Support, U.S. Gov't, P.H.S.