A novel dimeric dipeptide mimetic of the BDNF selectively activates the MAPK-Erk signaling pathway.

On the basis of the structure of beta-turn of loop 2 of brain-derived neurotrophic factor (BDNF), its new dimeric dipeptide mimetic bis-(N-hexanoyl-L-seryl-L-lysine) hexamethylenediamide (GTS-201) was created. It activated TrkB and Erk, did not activate Akt, and exhibited neuroprotective activity in vitro at concentrations of 10-5-10-8 M. Unlike the mimetics that activate Erk and Akt, GTS-201 did not exhibit antidepressant properties. For the manifestation of the antidepressant activity of BDNF mimetics, the activation of its both major signaling pathways is required.