Somatostatin analogs which define the role of the lysine‐9 amino group

Abstract
Structure-activity studies of the lysine residue in the highly active cyclic hexapeptide somatostatin analog cyclo(Pro-Phe-D-Trp-Lys-Thr-Phe) confirm the importance of the lysine amino group for biological activity through the loss of activity seen on replacement of lysine by ornithine, arginine, histidine and p-amino phenylalanine. Three analogs containing thialysine, .gamma.- and .delta.-fluorolysine were equipotent to the parent as inhibitors of insulin, glucagon, and growth hormone release in rats. The pKa''s of the amino groups in these equiactive peptides ranged from 8.23-9.4. The lack of a correlation between the basicity of the amino groups and the biological activities suggests that deprotonation is not required for biological activity.