Design and synthesis of a novel dipeptide mimetic of the 4^th loop of neurotrophin-3 and its pharmacological effects

A novel neurotrophin-3 loop 4 dipeptide mimetic, bis(N-y-hydroxybutyryl-l-glutamyl-l-asparagine) hexamethylenedi-amide (GTS-302), was designed and synthesized. Compound GTS-302 activated the tyrosine kinase receptors TrkC and TrkB, exhibited cytoprotective activity (10-8-10-5 M) in oxidative stress model in HT-22 cells and in 6-hydroxy-dopamine-induced SH-SY5Y cell damage. It also demon-strated an antidepressant-like activity in the forced swim test in mice (0.5-10.0 mg kg-1, intraperitoneally).