Linked Life Data

2666608

Source:http://linkedlifedata.com/resource/pubmed/id/2666608

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1989-8-30
pubmed:abstractText
We studied the peptide backbone modifications that improve the metabolic stability of the resulting peptides and yet retain high inhibitory activity against human plasma renin. A systematic investigation of N-alpha-methyl and C-alpha-methyl modifications at the P2 and P3 sites of renin-inhibitory peptides that contain part of the human angiotensinogen sequence led to the discovery of N-alpha-methyl amino acids at the P2 site as a useful structural modification. U-71,038 (11) inhibited human plasma renin with an in vitro potency (IC50) of 2.6 x 10(-10) mol/l. It is highly selective for renin and, as anticipated, resistant to proteolytic degradation. Additional study based on molecular graphic modelling has led us to propose a gamma-lactam conformational constraint at the P2-P3 site. This pseudo-dipeptide has proved useful in the preparation of active renin inhibitors. Compound 18a inhibited human plasma renin with an in vitro potency (IC50) of 2.1 x 10(-9) mol/l. This class of compounds also offers structural features for the study of enzyme-bound conformers.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0952-1178
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
S21-3
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Renin inhibitory peptides: a study of structural modifications in the peptide backbone.
pubmed:affiliation
Cardiovascular Diseases Research, Upjohn Company, Kalamazoo, Michigan 49001.
pubmed:publicationType
Journal Article