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

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.sup.-5 - 10.sup.-8 M in HT-22 immortalized hippocampal neuronal cell cul...

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Bibliographic Details
Published in:Pharmaceutical chemistry journal 2018-12, Vol.52 (9), p.763
Main Authors: Sazonova, N. M, Tarasyuk, A. V, Shumskii, A. N, Povarnina, P. Yu, Kruglov, S. V, Antipova, T. A, Gudasheva, T. A
Format: Article
Language:English
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Summary: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.sup.-5 - 10.sup.-8 M in HT-22 immortalized hippocampal neuronal cell culture under H.sub.2O.sub.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.
ISSN:0091-150X
DOI:10.1007/s11094-018-1896-0