Design and Synthesis of Cholecystokinin-4 Dipeptide Analogues with Anxiolytic and Anxiogenic Activities

T. A. Gudasheva1 #, E. P. Kir’yanova1, L. G. Kolik1, M. A. Konstantinopol’skii1 and S. B. Seredenin1

#Phone: (495) 601-23-73; fax: (495) 151-12-61; e-mail:

1Zakusov Research Institute of Pharmacology, Russian Academy of Medical Sciences, Baltiiskaya ul. 8, Moscow, 125315, Russia

Received: May 29, 2006;  in final form: June 15, 2006

Abstract.  A new series of dipeptide analogues of the general formula Ph(CH2)nCO-NH(CH2)mCO-Trp-NH2 (n = 1, 3–5; m = 1–3) was designed based on the structure of the endogenous tetrapeptide cholescystokinin-4 (CCK-4) and the topochemical Shemyakin-Ovchinnikov-Ivanov principle. The L-tryptophan derivatives exhibited anxiolytic properties and the D-tryptophan derivatives, anxiogenic properties. The dipeptide Ph(CH2)5CO-Gly-L-Trp-NH2 (GB-115) with the activity in rats of 0.05–0.2 mg/kg after oral and intraperitoneal administration was chosen for further studies as a promising anxiolytic agent.

Key words:  anxiolytic activity, CCK-4, CCK-4 analogues, cholecystokinin, design, dipeptides

Russian Journal of Bioorganic Chemistry 2007, 33 (4): 383-389