Non-reducible cyclic, and azaphenylalanyl6 analogues of somatostatin.
SSeven new analogues of somatostatin are described, along with the effects of these analogues on pentagastrin-stimulated gastric acid and pepsin secretion in conscious cats. Replacement of the cystine disulphide bridge of somatostatin with an amide bridge, with or without deletion of the N-terminal dipeptide, resulted in analogues with approximately 20% of the potency of somatostatin. Simultaneous ommision of Lys4 in the amide-bridge analogues reduced the activity of the peptides to approximately 5% of somatostatin. Substitution of Phe6 of somatostatin or an amide-bridged analogue with azaphenylalanyl resulted in peptides with no detectable activity. The results illustrate the possible importance of the basic side-chain of Lys4 for the activity of somatostatin. The lack of activity of azaphenylalanyl6 analogues of somatostatin demonstrate the extreme importance of the orientation of the side-chain of Phe6 for the activity of somatostatin, possibly for the binding to somatostatin receptors.
D000595:Amino Acid Sequence; D000818:Animals; D002415:Cats; D055598:Chemical Phenomena; D002621:Chemistry; D005750:Gastric Juice / Q000378:metabolism; D010434:Pepsin A / Q000037:antagonists & inhibitors; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D013004:Somatostatin; D010434:Pepsin A