Synthesis and Biological Properties of a New Dipeptide Mimetic of Brain-Derived Neurotrophic Factor Loop 2 **

dimeric dipeptide mimetic of brain-derived neurotrophic factor loop 2, bis -( N -hexanoyl-seryl-lysine) hexamethylenediamide or GTS-201, was designed and synthesized. It exhibited neuroprotective activity at concentrations of 10 –5 – 10 –8 M in HT-22 immortalized hippocampal neuronal cell culture under H 2 O 2 -induced oxidative stress. Western-blot analysis showed that it activated TrkB receptors and Erk but not Akt. GTS-201 did not exhibit antidepressant activity in a Porsolt forced swim test on BALB/c mice at i.p. doses of 0.1, 1.0, and 5.0 mg/kg, in contrast with previously synthesized GSB-106, a dimeric dipeptide mimetic of loop 4. The results confirmed the previous original hypothesis about the possible discrimination of neurotrophin functions by low-molecular-mass mimetics of their separate loops.