Synthesis and conformational study of a cyclic hexapeptide analog of somatostatin containing dehydrophenylalanine.
A cyclic hexapeptide analog of somatostatin, cyclo-(Pro-delta z-Phe-D-Trp-Lys-Thr-Phe) (II) has been synthesized by a combination of solid phase and solution methodology. It shows a potency for inhibition of growth hormone release in vitro about one-tenth that of the corresponding saturated analog, cyclo-(Pro-Phe-D-Trp-Lys-Thr-Phe) (I). N.m.r. studies indicate comparable backbone conformations for analogs I and II. However, the sum of our findings from biological evaluation and solution physical data suggest that on the receptor the position-7 phenyl ring of I is adopting a conformation which differs from that of one of the major solution conformers defined previously by n.m.r. studies.
D000818:Animals; D002942:Circular Dichroism; D005934:Glucagon / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism; D007202:Indicators and Reagents; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D010446:Peptide Fragments / Q000138:chemical synthesis*; D010649:Phenylalanine / Q000031:analogs & derivatives; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011487:Protein Conformation; D051381:Rats; D013004:Somatostatin / Q000138:chemical synthesis* / Q000031:analogs & derivatives; D013329:Structure-Activity Relationship
D007202:Indicators and Reagents; D007328:Insulin; D010446:Peptide Fragments; C040706:somatostatin, cyclo(Pro-dehydro-Phe-Trp-Lys-Thr-Phe); D010649:Phenylalanine; D013004:Somatostatin; C018632:phenyldehydroalanine; D013006:Growth Hormone; D005934:Glucagon