SYNTHESIS OF THE PHARMACOLOGICALLY ACTIVE ANALOG OF THE GSB-106, DIPEPTID MIMETIC OF BDNF

DOI: https://doi.org/10.29296/25877313-2019-07-01
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Issue: 
7
Year: 
2019

N.M. Sazonova к.х.н., Federal State Budgetary Institution «Research Zakusov Institute of Pharmacology» (Moscow) A.V. Tarasiuk Research Scientist, Federal State Budgetary Institution «Research Zakusov Institute of Pharmacology» (Moscow) E-mail: tarasiuk86@ gmail.com S.V. Nikitin Ph.D. (Chem.), Federal State Budgetary Institution «Research Zakusov Institute of Pharmacology» (Moscow) I.O. Logvinov Research Scientist, Federal State Budgetary Institution «Research Zakusov Institute of Pharmacology» (Moscow) A.G. Mezhlumyan Post-gradutete Student, Federal State Budgetary Institution «Research Zakusov Institute of Pharmacology» (Moscow) O.N. Vorontsova Ph.D. (Biol.), Federal State Budgetary Institution «Research Zakusov Institute of Pharmacology» (Moscow) P.Yu. Povarnina Ph.D. (Biol.), Federal State Budgetary Institution «Research Zakusov Institute of Pharmacology» (Moscow) T.A. Antipova Ph.D. (Biol.), Federal State Budgetary Institution «Research Zakusov Institute of Pharmacology» (Moscow) T.A. Gudasheva Dr.Sc. (Biol.), Professor, Correspondent Member of RAS, Federal State Budgetary Institution «Research Zakusov Institute of Pharmacology» (Moscow) S.B. Seredinin Dr.Sc. (Med.), Professor, Academician of RAS, Federal State Budgetary Institution «Research Zakusov Institute of Pharmacology» (Moscow)

Previously the dimeric dipeptide mimetic bis-(N-monosuccinil-L-seryl-L-lysine) hexamethylenediamide (GSB-106) was created in Zakusov Institute of Pharmacology. GSB-106 demonstrates neuroprotective activity in vitro under oxidative stress conditions in concentrations of 10–5–10–7 M and also it demonstrates antidepressant activity in behavioral tests in rodents i.p. in the doses of 0.1–1.0 mg/kg. The acetyl analog of GSB-106, bis-(N-acetyl-L-seryl-L-lysine) hexamethylenediamide (GTS-106Ac), was synthesized to study the role of the N-acyl radical in the activity of the GSB-106. The study of the neuroprotective activity of GTS-106Ac on the neuronal HT-22 culture under conditions of oxidative stress showed this activity in concentrations of 10–5–10–8 M. In the test of Porsolt in mice, i.p., GTS-106Ac showed the antidepressant effect in the doses of 1.0 and 5.0 mg/kg, significantly reducing the time of immobility of the animals compared with control group of animals.

Keywords: 
BDNF
mimetic
dipeptide
GSB-106
GTS-106Ac
neuroprotective activity
antidepressant activity
peptide synthesis

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