Abstract
The possible mechanisms of ligand–receptor binding of arginine-containing tetrapeptides with the NaV1.8 channels in the primary sensory neuron were investigated. Ac-RERR-NH2 tetrapeptide, acting outside the neuronal membrane, was found to decrease voltage sensitivity of the examined channels. In contrast, the Ac-REАR-NH2 tetrapeptide did not exhibit the same effect. Conformational analysis was used to investigate the mechanisms of ligand–receptor binding of a number of studied short peptides; it suggested that positively charged guanidine side chains of two arginine residues played a key role in peptide binding. Another amino-acid residue (glutamic acid) should be located between these two arginine residues. Our calculations demonstrated that the mechanism of ligand–receptor binding could not be implemented if the distance between the guanidine groups in short peptide molecules was less than a defined threshold value. The results allow one to conclude that the Ac-RERR-NH2 tetrapeptide and several other peptides capable of binding with the NaV1.8 channel by the same molecular mechanism have the potential to become novel peripheral analgesic drugs.
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The research was conducted within a World-Class Research Center program and received funding from the Ministry of Education and Science of the Russian Federation (agreement no. 075-15-2020-921, November 13, 2020).
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Translated by E. Sherstyuk
Abbreviations: AI, area index.
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Rogachevsky, I.V., Kalinina, A.D., Penniyaynen, V.A. et al. A Possible Mechanism of Modulation of Slow Sodium Channels in the Sensory Neuron Membrane by Short Peptides. BIOPHYSICS 66, 579–588 (2021). https://doi.org/10.1134/S0006350921040205
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DOI: https://doi.org/10.1134/S0006350921040205