Conformational modifications of cyclic hexapeptide somatostatin analogs.
A model for the bioactive conformation of the highly active cyclic hexapeptide somatostatin analog cyclo-(Pro-Phe-D-Trp-Lys-Thr-Phe) has been proposed. As a test of this model, several compounds containing lactam and N-Me amino acid conformational modifications in the Thr-Phe-Pro-Phe beta turn were synthesized. The N-Me alanine and sarcosine substitutions for proline gave highly active analogs, while lactam dipeptides in place of Phe-Pro decreased potency. 1H n.m.r. and CD spectra of these analogs illustrate the conformational effects in solution of these modifications. The results provide additional support for the proposed conformational model.
D000818:Animals; D002942:Circular Dichroism; D005934:Glucagon / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000494:pharmacology; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011487:Protein Conformation; D051381:Rats; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D007328:Insulin; D010446:Peptide Fragments; C040704:cyclo(Pro-Phe-Trp-Lys-Thr-Phe); D013004:Somatostatin; D013006:Growth Hormone; D005934:Glucagon