Somatostatin analogs which define the role of the lysine-9 amino group.
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. 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.
D001681:Biological Assay; D002942:Circular Dichroism; D006728:Hormones; D008239:Lysine; D009682:Magnetic Resonance Spectroscopy; D013004:Somatostatin / Q000031:analogs & derivatives*; D013329:Structure-Activity Relationship
D006728:Hormones; D013004:Somatostatin; D008239:Lysine