An Expedient Synthesis of Flexible Nucleosides through Enzymatic Glycosylation of Proximal and Distal Fleximer Bases

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dc.contributor.authorVichier‐Guerre, Sophie
dc.contributor.authorKu, Therese C.
dc.contributor.authorPochet, Sylvie
dc.contributor.authorSeley-Radtke, Katherine
dc.date.accessioned2020-03-04T19:48:26Z
dc.date.available2020-03-04T19:48:26Z
dc.date.issued2020-01-03
dc.description.abstractThe structurally unique “fleximer” nucleosides were originally designed to investigate how flexibility in a nucleobase could potentially affect receptor–ligand recognition and function. Recently they have been shown to have low‐to‐sub‐micromolar levels of activity against a number of viruses, including coronaviruses, filoviruses, and flaviviruses. However, the synthesis of distal fleximers in particular has thus far been quite tedious and low yielding. As a potential solution to this issue, a series of proximal fleximer bases (flex‐bases) has been successfully coupled to both ribose and 2′‐deoxyribose sugars by using the N‐deoxyribosyltransferase II of Lactobacillus leichmannii (LlNDT) and Escherichia coli purine nucleoside phosphorylase (PNP). To explore the range of this facile approach, transglycosylation experiments on a thieno‐expanded tricyclic heterocyclic base, as well as several distal and proximal flex‐bases were performed to determine whether the corresponding fleximer nucleosides could be obtained in this fashion, thus potentially significantly shortening the route to these biologically significant compounds. The results of those studies are reported herein.en_US
dc.description.sponsorshipThe authors from the IP would like to thank FrØdØric Bonhomme (UMR3523) for assisting with HRMS analysis and Drs. Bruno Vi-torge and Inaki Guijarro (BioNMR platform) for providing access to Avance 600 and Avance Neo 800 spectrometers. This work was funded by the Institut Pasteur and the Centre National de la Recherche Scientifique (CNRS; S.V.-G. and S.P.) and the National Institutes of Health/NIAID R21 AI118470-01 (K.S.-R.) and T32GM066706 (K.S.-R. and T.K.).en_US
dc.description.urihttps://onlinelibrary.wiley.com/doi/full/10.1002/cbic.201900714en_US
dc.format.extent7 pagesen_US
dc.genrejournal articles postprintsen_US
dc.identifierdoi:10.13016/m2ncpp-rfon
dc.identifier.citationVichier‐Guerre, Sophie; Ku, Therese C.; Pochet, Sylvie; Seley‐Radtke, Katherine L.; An Expedient Synthesis of Flexible Nucleosides through Enzymatic Glycosylation of Proximal and Distal Fleximer Bases; ChemBioChem (2020); https://onlinelibrary.wiley.com/doi/full/10.1002/cbic.201900714en_US
dc.identifier.urihttps://doi.org/10.1002/cbic.201900714
dc.identifier.urihttp://hdl.handle.net/11603/17485
dc.language.isoen_USen_US
dc.publisherWiley Online Libraryen_US
dc.relation.isAvailableAtThe University of Maryland, Baltimore County (UMBC)
dc.relation.ispartofUMBC Chemistry & Biochemistry Department Collection
dc.relation.ispartofUMBC Faculty Collection
dc.rightsThis item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.
dc.rightsAccess to this item will begin on 2021-01-03
dc.rightsThis is the peer reviewed version of the following article: Vichier‐Guerre, Sophie; Ku, Therese C.; Pochet, Sylvie; Seley‐Radtke, Katherine L.; An Expedient Synthesis of Flexible Nucleosides through Enzymatic Glycosylation of Proximal and Distal Fleximer Bases; ChemBioChem (2020); https://onlinelibrary.wiley.com/doi/full/10.1002/cbic.201900714, which has been published in final form at https://doi.org/10.1002/cbic.201900714. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
dc.titleAn Expedient Synthesis of Flexible Nucleosides through Enzymatic Glycosylation of Proximal and Distal Fleximer Basesen_US
dc.typeTexten_US

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