A bioactive somatostatin analog-without a type II ' beta-turn: Synthesis and conformational analysis in solution

A cyclic somatostatin analog [GRAPHICS] (1) has been synthesized. Biological assays show that this compound has str ong binding affinities to somatostatin hsst2 and hsst5 receptor subtypes (5 .2 and 1.2 nM, respectively, and modest affinity to hsst4 (41.1 nM)). Our c onformational analysis carried out in DMSO-d(6) indicates that this compoun d exists as two structures arising from the trans and cis configurations of the peptide bond between Phe(7) and N-alkylated Gly(8). However, neither c onformer exhibits a type II' beta -turn. This is the first report of a pote nt bioactive somatostatin analog that does riot exhibit a type II' beta -tu rn in solution. Molecular dynamics simulations (500 ps) carried out at 300 K indicate that the backbone of compound 1 is more flexible than other cycl ic somatostatin analogs formed by disulfide bonds. Copyright (C) 2001 Europ ean Peptide Society and John Wiley & Sons, Ltd.