Linked Life Data

3184127

Source:http://linkedlifedata.com/resource/pubmed/id/3184127

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1988-12-5
pubmed:abstractText
Investigations were directed toward inhibition of an aminopeptidase, isolated from rat brain, which has been implicated in the metabolic inactivation of enkephalins. The design rationale and synthesis of novel peptidyl diamino thiol inhibitors of rat brain aminopeptidase are presented, along with accompanying structure-activity analysis. Some of the reported compounds are highly active aminopeptidase inhibitors and possess enzyme inhibitory potency in the nanomolar range (62; I50 = 1 nM). Analysis of the data permits speculations on possible modes of binding of diamino thiols to aminopeptidase. Other investigations were directed toward understanding the mode of enzyme binding of the naturally occurring aminopeptidase inhibitor bestatin. On the basis of published models of enzyme binding, replacement of the C-2 hydroxyl group of bestatin by a sulfhydryl group was anticipated to lead to enhanced inhibition due to a strengthened interaction of this group with enzymic zinc. Contrary to expectations, "thiobestatin" inhibited rat brain aminopeptidase with only the same degree of effectiveness as the corresponding alcohol. Speculations on the possible mode of enzyme-inhibitor binding of bestatin are offered.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2199-211
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
Design of novel inhibitors of aminopeptidases. Synthesis of peptide-derived diamino thiols and sulfur replacement analogues of bestatin.
pubmed:affiliation
Squibb Institute for Medical Research, Princeton, New Jersey 08543-4000.
pubmed:publicationType
Journal Article