A gastrin-releasing peptide antagonist containing A psi (CH2O) amide bond surrogate.
The [Leu26-psi(CH2O)Leu27] derivative of N-Ac-GRP20-27-peptide amide was prepared and evaluated as a gastrin-releasing peptide antagonist. This psi(CH2O) derivative was found to be a more potent inhibitor of [3H-Phe15]GRP15-24NH2 binding and N-Ac-GRP20-27NH2 induced mitogenesis in Swiss 3T3 fibroblasts than the related nitrogen analog [Leu13-psi(CH2NH)Leu14] bombesin. Possible reasons for the improved activity of the (CH2O) insert relative to the (CH2NH) group include increased hydrophobicity and a reduced tendency of the oxygen derivative to form hydrogen bonds.
Saari
W S
WS
Department of Medicinal Chemistry, Merck Sharp & Dohme Research Laboratory, West Point, Pennsylvania 19486.
Heimbrook
D C
DC
Friedman
A
A
Fisher
T W
TW
Oliff
A
A
D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D019886:Gastrin-Releasing Peptide; D005768:Gastrointestinal Hormones / Q000037:antagonists & inhibitors*; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D010455:Peptides / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay; D013329:Structure-Activity Relationship
D005768:Gastrointestinal Hormones; D010446:Peptide Fragments; D010455:Peptides; C061982:gastrin releasing peptide (20-27), N-acetyl-Leu(26)-psi(CH2O)Leu(27)-; D019886:Gastrin-Releasing Peptide