Synthesis and Biological Evaluation of Mixed β²/β³-Dipeptides as Somatostatin Analogs

Abstract

Somatostatin (somatotropin release-inhibiting factor, SRIF) is a widely distributed tetradecapeptide with multiple functions, including modulation of secretion of growth hormone, insulin, glucagon, and gastric acid. The mechanism of action of somatostatin is mediated by specific membrane receptors, and to date five individual receptor subtypes have been characterized and cloned (hsstl-5). Extensive studies with synthetic Somatostatin analogues have established that the key pharmacophoric element of SRIF₁₄ includes Phe⁷-Trp⁸-Lys⁹-Thr¹⁰, which comprise a ß-turn [1]. This secondary structural motif is often encountered in biologically active peptides, and is therefore an important target for mimicry in medicinal chemistry. Herein we report the synthesis and the biological evaluation of ß²-/ß³-mixed dipeptides as mimics of the crucial ß-turn region present in somatostatin.