A BACKBONE-CYLIC, RECEPTOR 5-SELECTIVE SOMATOSTATIN ANALOG - SYNTHESIS, BIOACTIVITY, AND NUCLEAR-MAGNETIC-RESONANCE CONFORMATIONAL-ANALYSIS

Cyclo(PheN2-Tyr-D-Trp-Lys-Val-PheC3)-Thr-NH2 (PTR 3046), a backbone-cy clic somatostatin analogue, was synthesized by solid-phase methodology . The binding characteristics of PTR 3046 to the different somatostati n receptors, expressed in CHO cells, indicate high selectivity to the SSTR5 receptor. PTR 3046 is highly stable against enzymatic degradatio n as determined in vitro by incubation with rat renal homogenate and h uman serum. The biological activity of PTR 3046 in vivo was determined in rats. PTR 3046 inhibits bombesin-and caerulein-indueed amylase and lipase release from the pancreas without inhibiting growth hormone or glucagon release. The major conformation of PTR 3046 in CD3OH, as det ermined by NMR, is defined by a type II' beta-turn at D-Trp-Lys and a cis amide bond at Val-PheC3.