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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
|
| pubmed:dateCreated |
1996-7-18
|
| pubmed:abstractText |
We report here on the synthesis and pharmacological properties of a new series of small linear and cyclic peptides derived from the five C-terminal amino acid residues of second-generation bradykinin receptor antagonists. Variations of the two first residues of the pentapeptide (Thi-Ser-D-Tic-Oic-Arg) were shown to modulate the biological activities of the analogs on bradykinin-induced smooth muscle contractions in rabbit jugular vein (RJV), a tissue preparation specific of the B2 bradykinin receptor. Several analogs showed pA2 values around 7 on this tissue preparation, and one cyclic compound, c[-Gly-Thi-D-Tic-Oic-Arg-], 24, in which Thi-Ser was replaced by Gly-Thi, displayed a pA2 of 7.4 on RJV. On the basis of these results, three cyclic molecules and their linear counterparts (compounds 22-24 and 4-6, respectively) were tested on human umbilical vein, a tissue specific of the human B2 receptor. The pKB values obtained for these compounds on these tissue preparations were equivalent to those obtained for the decapeptide NPC 567 (4.8 < pA2 < 5.1). NMR and molecular modeling studies performed on compound 24 clearly demonstrated a type II' beta-turn structure. This analog may serve as a new lead for the design of nonpeptide ligands of the bradykinin B2 receptor subtype.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
May
|
| pubmed:issn |
0022-2623
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
10
|
| pubmed:volume |
39
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
2095-101
|
| pubmed:dateRevised |
2004-11-17
|
| pubmed:meshHeading |
pubmed-meshheading:8642569-Amino Acid Sequence,
pubmed-meshheading:8642569-Animals,
pubmed-meshheading:8642569-Drug Design,
pubmed-meshheading:8642569-Humans,
pubmed-meshheading:8642569-Magnetic Resonance Spectroscopy,
pubmed-meshheading:8642569-Molecular Sequence Data,
pubmed-meshheading:8642569-Muscle, Smooth, Vascular,
pubmed-meshheading:8642569-Muscle Contraction,
pubmed-meshheading:8642569-Peptides, Cyclic,
pubmed-meshheading:8642569-Rabbits,
pubmed-meshheading:8642569-Receptors, Bradykinin
|
| pubmed:year |
1996
|
| pubmed:articleTitle |
Design and synthesis of new linear and cyclic bradykinin antagonists.
|
| pubmed:affiliation |
Institute de Recherches Servier, Suresnes, France.
|
| pubmed:publicationType |
Journal Article
|