A novel dimeric dipeptide mimetic of the BDNF selectively activates the MAPK-Erk signaling pathway

• Published in: Doklady. Biochemistry and biophysics Vol. 476; no. 1; pp. 291 - 295
• Main Authors: Gudasheva, T. A., Tarasiuk, A. V., Sazonova, N. M., Povarnina, P. Yu, Antipova, T. A., Seredenin, S. B.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01-09-2017; Springer Nature B.V
• Subjects: AKT protein; Animals; Biochemistry; Biological and Medical Physics; Biomedical and Life Sciences; Biophysics; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - chemistry; Cell Line; Dimerization; Dipeptides - chemistry; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - metabolism; Life Sciences; Lysine; MAP kinase; MAP Kinase Kinase Kinase 5 - drug effects; Mice; Molecular Biology; Neuroprotection; Neuroprotective Agents - chemistry; Neuroprotective Agents - pharmacology; Peptides; Peptidomimetics - chemistry; Peptidomimetics - pharmacology; Receptor, trkB - metabolism; Signal transduction; Signaling; TrkB receptors
• ISSN: 1607-6729; 1608-3091
• DOI: 10.1134/S1607672917050027

On the basis of the structure of beta-turn of loop 2 of brain-derived neurotrophic factor (BDNF), its new dimeric dipeptide mimetic
bis
-(
N
-hexanoyl-
L
-seryl-
L
-lysine) hexamethylenediamide (GTS-201) was created. It activated TrkB and Erk, did not activate Akt, and exhibited neuroprotective activity in vitro at concentrations of 10
–5
–10
–8
M. Unlike the mimetics that activate Erk and Akt, GTS-201 did not exhibit antidepressant properties. For the manifestation of the antidepressant activity of BDNF mimetics, the activation of its both major signaling pathways is required.