Email this article Docking of highly selective 5-HT2A/C receptor peptide ligands with antipsychotic activity
- Authors: Orlova A.B.1, Sventitskaya A.M.1, Vengerovich N.G.1,2, Nikiforov A.S.1, Ivanov I.M.1, Proshina Y.A.1
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Affiliations:
- State Research Testing Institute of Military Medicine of the Ministry of Defense of the Russian Federation
- Saint Petersburg State Chemical and Pharmaceutical University of the Ministry of Health of the Russian Federation
- Issue: Vol 3, No 1 (2021)
- Pages: 10-17
- Section: Pharmaceutical Sciences
- URL: https://ogarev-online.ru/PharmForm/article/view/61345
- DOI: https://doi.org/10.17816/phf61345
- ID: 61345
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Abstract
Search for new ligands selective to different subtypes of 5-HT2 receptors is an important scientific and practical problem for experimental psychopharmacology and clinical medicine. The majority of existing antagonists of the 5-HT2A and 5-HT2C subtypes possess all necessary anti-anxiety and antipsychotic properties, though they are partially selective to 5-HT2B receptors. Their activation leads to cardiotoxic side effects, so it significantly limits clinical application of these drugs.
For the search of new highly selective ligands of 5-HT2A/C receptors, an in silico screening algorithm was proposed using PScore.Max and Affinity.maxPScore parameters, which included the affinity of low molecular weight compounds for each 5-HT2 receptor subtype. Cyclic physiologically active substances of peptide nature have been proposed as new promising drugs with antipsychotic activity. Based on the CXXC library, a number of cyclopeptides with a high selectivity of structure to target binding sites were selected for further in vitro studies by extending of the peptide chain.
It was also found that a promising direction for increasing the selectivity of peptide ligands to 5-HT2A/C receptors is the introduction of non-proteinogenic amino acids during the formation of an initial docking library. The choice of these amino acids will be due to the nature of interactions between the reference ligands and amino acid residues of the binding site.
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##article.viewOnOriginalSite##About the authors
Anastasia B. Orlova
State Research Testing Institute of Military Medicine of the Ministry of Defense of the Russian Federation
Author for correspondence.
Email: gniiivm_15@mil.ru
SPIN-code: 6062-6074
Junior Research Fellow, State Scientific Research Testing Institute of Military Medicine of the Ministry of Defense of the Russian Federation
Russian Federation, Saint-PetersburgAlevtina M. Sventitskaya
State Research Testing Institute of Military Medicine of the Ministry of Defense of the Russian Federation
Email: gniiivm_15@mil.ru
Junior Research Fellow, State Scientific Research Testing Institute of Military Medicine of the Ministry of Defense of the Russian Federation
Russian Federation, Saint-PetersburgNikolay G. Vengerovich
State Research Testing Institute of Military Medicine of the Ministry of Defense of the Russian Federation; Saint Petersburg State Chemical and Pharmaceutical University of the Ministry of Health of the Russian Federation
Email: nikolai.vengerovich@pharminnotech.com
ORCID iD: 0000-0003-3219-341X
Doctor of Medicine (MD), Deputy Head of the Scientific Department, State Scientific Research Testing Institute of Military Medicine of the Ministry of Defense of the Russian Federation; Professor at the Industrial Ecology Department, Saint Petersburg State Chemical and Pharmaceutical University
Russian Federation, Saint-Petersburg; Saint-PetersburgAleksandr S. Nikiforov
State Research Testing Institute of Military Medicine of the Ministry of Defense of the Russian Federation
Email: gniiivm_15@mil.ru
D.Sc. in Biology, Senior Researcher, State Scientific Research Testing Institute of Military Medicine of the Ministry of Defense of the Russian Federation
Russian Federation, Saint-PetersburgIgor M. Ivanov
State Research Testing Institute of Military Medicine of the Ministry of Defense of the Russian Federation
Email: gniiivm_15@mil.ru
SPIN-code: 1518-3306
Ph.D in Medicine, Head of the Scientific Department, State Scientific Research Testing Institute of Military Medicine of the Ministry of Defense of the Russian Federation
Russian Federation, Saint-PetersburgYlia A. Proshina
State Research Testing Institute of Military Medicine of the Ministry of Defense of the Russian Federation
Email: gniiivm_15@mil.ru
Research Fellow of the Scientific Department, State Scientific Research Testing Institute of Military Medicine of the Ministry of Defense of the Russian Federation
Russian Federation, Saint-PetersburgReferences
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