The First Dipeptide Mimetic of Neurotrofin-3: Design and Pharmacological Properties
Т. А. Гудашева, Н. М. Сазонова, Алексей Валерьевич Тарасюк, И. О. Логвинов, Т. А. Антипова, Д. М. Никифоров, P. Yu. Povarnina, С. Б. Середенин
Abstract
The dimeric dipeptide mimetic hexamethylenediamide bis-(N-monosuccinyl-L-asparaginyl-L-asparagine) (GTS-301) was created on the basis of the structure of the exposed region of the neurotrophin-3 4th loop. The new compound, as well as the full-length neurotrophin, activated the TrkC and TrkB receptors. GTS-301 showed neuroprotective activity in experiments on HT-22 mouse hippocampal cells under conditions of oxidative stress and glutamate toxicity at concentrations of 10–12 and 10–8 M, respectively, and antidepressant-like activity in the forced swimming test on mice with 7-day intraperitoneal administration in doses of 10–40 mg/kg.