Short peptide with an inhibitory activity on the NMDA/Gly-induced currents

ABSTRACT

N-methyl-D-aspartate (NMDA) receptors are considered to be one of the most promising targets for treatment-resistant depression. The majority of known ligands may cause undesirable side-effects, except tetrapeptide rapastinel which demonstrated rapid antidepressant effect without psychotomimetic side effects. High shape similarity was noticed between dipeptide Phe-Tyr and NMDA receptor non-competitive antagonist ifenprodil which imply the possibility for antagonistic action of this peptide. A series of analogs were selected based on the docking results and molecular dynamics simulations. A dipeptide D-Phe-L-Tyr showed modest inhibitory activity comparable to rapastinel.

KEYWORDS:

• Neuroactive peptides
• glutamate receptors
• molecular dynamics simulations
• patch clamp
• radioligand studies

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Russian Science Foundation under Grant № 18-75-00077.