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Chiral discrimination of cyclodecapeptide to anti-COVID-19 clinical candidates: a theoretical study

Various undesirable side effects are frequently associated with isomers of chiral clinical agents. The separation of chiral medicines remains a challenging issue in the medicines research. In this work, we employed cyclic decapeptide as the host molecule and the M06-2X theoretical computational meth...

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Detalles Bibliográficos
Autores principales: Yang, Jian, Wang, Xinqing, Ji, Shuangshuang, Zhu, Yanyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10011793/
https://www.ncbi.nlm.nih.gov/pubmed/37363041
http://dx.doi.org/10.1007/s11224-023-02149-5
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author Yang, Jian
Wang, Xinqing
Ji, Shuangshuang
Zhu, Yanyan
author_facet Yang, Jian
Wang, Xinqing
Ji, Shuangshuang
Zhu, Yanyan
author_sort Yang, Jian
collection PubMed
description Various undesirable side effects are frequently associated with isomers of chiral clinical agents. The separation of chiral medicines remains a challenging issue in the medicines research. In this work, we employed cyclic decapeptide as the host molecule and the M06-2X theoretical computational method for chiral recognition of four clinical candidate guests and their isomers, including bucillamine, molnupiravir, azvudine, and VV116, which are relevant for the treatment of COVID-19. The obtained results indicated that bucillamine and molnupiravir and their respective isomers may be distinguished by cyclic decapeptide and that some of the isomers of Azvudine and VV116 may be discriminated by cyclic decapeptide. The inclusion conformation, deformation analysis, and electrostatic potential analysis also visualized the binding modes and binding sites between cyclic peptides and medicine candidates. A series of weak interaction analyses suggest that hydrogen bonding and dispersion interactions may be the primary factors for the recognition and separation of the clinical candidates by cyclic decapeptides. Visualized analyses of noncovalent interaction, hydrogen bond interaction, and NBO, AIM topological demonstrated that the difference of dispersion interaction is not obvious between the complexes, while the type and number of hydrogen bonds are very different, hinting that hydrogen bonds might be crucial for the differentiation of molnupiravir and its isomers. These findings might provide a theoretical reference for the identification and separation of chiral compounds in host–guest interaction. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11224-023-02149-5.
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spelling pubmed-100117932023-03-14 Chiral discrimination of cyclodecapeptide to anti-COVID-19 clinical candidates: a theoretical study Yang, Jian Wang, Xinqing Ji, Shuangshuang Zhu, Yanyan Struct Chem Research Various undesirable side effects are frequently associated with isomers of chiral clinical agents. The separation of chiral medicines remains a challenging issue in the medicines research. In this work, we employed cyclic decapeptide as the host molecule and the M06-2X theoretical computational method for chiral recognition of four clinical candidate guests and their isomers, including bucillamine, molnupiravir, azvudine, and VV116, which are relevant for the treatment of COVID-19. The obtained results indicated that bucillamine and molnupiravir and their respective isomers may be distinguished by cyclic decapeptide and that some of the isomers of Azvudine and VV116 may be discriminated by cyclic decapeptide. The inclusion conformation, deformation analysis, and electrostatic potential analysis also visualized the binding modes and binding sites between cyclic peptides and medicine candidates. A series of weak interaction analyses suggest that hydrogen bonding and dispersion interactions may be the primary factors for the recognition and separation of the clinical candidates by cyclic decapeptides. Visualized analyses of noncovalent interaction, hydrogen bond interaction, and NBO, AIM topological demonstrated that the difference of dispersion interaction is not obvious between the complexes, while the type and number of hydrogen bonds are very different, hinting that hydrogen bonds might be crucial for the differentiation of molnupiravir and its isomers. These findings might provide a theoretical reference for the identification and separation of chiral compounds in host–guest interaction. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11224-023-02149-5. Springer US 2023-03-14 /pmc/articles/PMC10011793/ /pubmed/37363041 http://dx.doi.org/10.1007/s11224-023-02149-5 Text en © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Research
Yang, Jian
Wang, Xinqing
Ji, Shuangshuang
Zhu, Yanyan
Chiral discrimination of cyclodecapeptide to anti-COVID-19 clinical candidates: a theoretical study
title Chiral discrimination of cyclodecapeptide to anti-COVID-19 clinical candidates: a theoretical study
title_full Chiral discrimination of cyclodecapeptide to anti-COVID-19 clinical candidates: a theoretical study
title_fullStr Chiral discrimination of cyclodecapeptide to anti-COVID-19 clinical candidates: a theoretical study
title_full_unstemmed Chiral discrimination of cyclodecapeptide to anti-COVID-19 clinical candidates: a theoretical study
title_short Chiral discrimination of cyclodecapeptide to anti-COVID-19 clinical candidates: a theoretical study
title_sort chiral discrimination of cyclodecapeptide to anti-covid-19 clinical candidates: a theoretical study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10011793/
https://www.ncbi.nlm.nih.gov/pubmed/37363041
http://dx.doi.org/10.1007/s11224-023-02149-5
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