Synthesis and conformational study of two cyclic analogues of somatostatin containing an AMPA-spacer unit.
Two cyclic somatostatin analogues containing the active sequence Phe7-D-Trp8-Lys9-Thr10 and a meta- or para-(aminomethyl) phenylacetic acid (AMPA) spacer unit, have been synthesized. A conformational study using 2D n.m.r. techniques (COSY, NOESY) reveals that the conformation of the meta-AMPA analogue has some analogy with the bio-active conformation proposed earlier by Veber and colleagues, while in the para-AMPA analogue an equilibrium exists between a beta-II' turn and a gamma-turn structure. Both analogues show no GH-inhibition or LH-inhibition in in vitro assays.
D000818:Animals; D002478:Cells, Cultured; D013006:Growth Hormone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011487:Protein Conformation
D007202:Indicators and Reagents; C053147:cyclo-(phenylalanyl-tryptophyl-lysyl-threonyl-3-(aminomethyl)phenylacetic acid); C053148:cyclo(phenylalanyl-tryptophyl-lysyl-threonyl-4-(aminomethyl)phenylacetic acid); D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone