Synthesis and Biological Properties of a New Dipeptide Mimetic of Brain-Derived Neurotrophic Factor Loop 2**
- Authors: Sazonova N.M.1, Tarasyuk A.V.1, Shumskii A.N.1, Povarnina P.Y.1, Kruglov S.V.1, Antipova T.A.1, Gudasheva T.A.1, Seredenin S.B.1
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Affiliations:
- V. V. Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
- Issue: Vol 52, No 9 (2018)
- Pages: 763-770
- Section: Article
- URL: https://journals.rcsi.science/0091-150X/article/view/245455
- DOI: https://doi.org/10.1007/s11094-018-1896-0
- ID: 245455
Cite item
Abstract
A 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 H2O2-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.
About the authors
N. M. Sazonova
V. V. Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
Author for correspondence.
Email: saz-nellya@mail.ru
Russian Federation, 8 Baltiiskaya, Moscow, 125315
A. V. Tarasyuk
V. V. Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
Email: saz-nellya@mail.ru
Russian Federation, 8 Baltiiskaya, Moscow, 125315
A. N. Shumskii
V. V. Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
Email: saz-nellya@mail.ru
Russian Federation, 8 Baltiiskaya, Moscow, 125315
P. Yu. Povarnina
V. V. Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
Email: saz-nellya@mail.ru
Russian Federation, 8 Baltiiskaya, Moscow, 125315
S. V. Kruglov
V. V. Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
Email: saz-nellya@mail.ru
Russian Federation, 8 Baltiiskaya, Moscow, 125315
T. A. Antipova
V. V. Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
Email: saz-nellya@mail.ru
Russian Federation, 8 Baltiiskaya, Moscow, 125315
T. A. Gudasheva
V. V. Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
Email: saz-nellya@mail.ru
Russian Federation, 8 Baltiiskaya, Moscow, 125315
S. B. Seredenin
V. V. Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences
Email: saz-nellya@mail.ru
Russian Federation, 8 Baltiiskaya, Moscow, 125315