Synthesis and conformational study of a cyclic hexapeptide analog of somatostatin containing dehydrophenylalanine

Abstract
A cyclic hexapeptide analog of somatostatin, cyclo-(Pro-.DELTA.z-Phe-D-Trp-Lys-Thr-Phe) (II) was synthesized by a combination of solid phase and solution methodology. It shows a potency for inhibition of [rat] growth hormone release in vitro .apprx. 1/10 that of the corresponding saturated analog, cyclo-(Pro-Phe-D-Trp-Lys-Thr-Phe) (I). NMR studies indicate comparable backbone conformations for analogs I and II. However, the sum of the 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 NMR studies.

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