Somatostatin analogs. Relative importance of the disulfide bridge and of the Ala-Gly side chain for biological activity.

Four analogs of ovine somatostatin (SRIF, PSOMATOTROPIN RELEASE INhibiting factor), the sequence of which is H-Ala-Gly-Cys-Lys-Asn-Phe-Phe-trp-Lys-Thr-Phe-Thr-Ser-Cys-OH, have been synthesized by the solid-phase methodology. The compounds were assayed and were found to possess the following somatotropin release inhibiting potencies relative to pure synthetic somatostatin in vitro and in vivo, respectively: [Ala3,14]somatostatin, 0.6 and 2.0%; [SMe-Cys3,14]somatostatin, 4 and 0.6%; [NAc-Cys3]somatostatin, 39 and 105%; [des-Ala1-Gly2]somatostatin, 65 and 71%. The dihydrosomatostatin analogs [NAc-Cys3-H2]somatostatin and [des-Ala1Gly2-H2]somatostatin after two purifications by gel filtration were assessed to be at least 80% homogeneous and had respectively 99 and 89% of somatostatin potencied in vivo. Structure-activity relationships are discussed.