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Vol. 23, Art. 44 (pp. 733-747)    |    2022       

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Search for cyclic peptide ligands of peripheral n-cholinergic receptors using chemoinformatics methods

Ivanov I.М., Orlova A.B., Neeshpapa А.D., Nikiforov A.S., Chepur S.V.

FSBI «State Research Testing Institute of Military Medicine» of the Ministry of Defense of the Russian Federation, 195043, Saint-Petersburg, Russia

Brief summary

The muscle-type N-cholinergic receptor (NCR) is an important biological target in the development of therapeutic agents, in particular for the treatment of myasthenia gravis and the recovery of neuromuscular block after the use of muscle relaxants. Using the Torpedo marmorata NCR model, virtual screening of libraries of cyclic peptides up to 8 amino acids in length containing one SS bond was carried out. We selected 7 samples with predicted properties of ligands of the orthosteric acetylcholine binding site of peripheral N-cholinergic receptors with high rates of correspondence to reference compounds according to the pattern of interaction with the target. Among the samples synthesized by the solid-phase method on the model of experimental myasthenia gravis in rats, the greatest therapeutic effect was noted in the GRCWRCYW according to the criteria for keeping animals on an inverted grid and the duration of treadmill running.


Key words

myasthenia gravis, N-cholinergic receptor, peptides, solid-phase synthesis, molecular docking, chemoinformatics.

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