Synthesis of somatostatin analogs resistant to the action of trypsin

The synthesis of a series of octapeptides based on the somatostatin analog cyclo(-Asn-Phe-Phe-D-Trp-Lys-Thr-Phe-Gaba-) containing the substitutions [Aap9], [D-Lys9], [L-Trp8, D-Lys9], [L-Orn9] and [D-aThr10] is reported. The analogs were designed and have been shown to inhibit proteolysis at the proposed (1) primary cleavage site between Lys9-Thr10 and thereby increase their stability to enzymic attack.