Novel sst5-selective somatostatin dicarba-analogs: Synthesis and conformation-affinity relationships

We describe synthesis, conformational studies, and binding to the five somatostatin receptors (sst 1-5) of a few analogues of the cyclic octapeptide octreotide, where the disulfide bridge was replaced by a dicarba group. Binding experiments showed that two analogues had good affinity and high selectivity for the sst5 receptor. Three-dimensional structures of the active analogues were determined by (1)H NMR spectroscopy. Helical propensities well correlates with the peptide sst5 affinity. Finally, a new pharmacophore model for the sst5 was developed.