Alpha-carboxynucleoside phosphonates: direct-acting inhibitors of viral DNA polymerases

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dc.contributor.authorBalzarini, Jan
dc.contributor.authorFord, Alan
dc.contributor.authorMaguire, Nuala M.
dc.contributor.authorJohn, Jubi
dc.contributor.authorDas, Kalyan
dc.contributor.authorArnold, Eddy
dc.contributor.authorDehaen, Wim
dc.contributor.authorMaguire, Anita R.
dc.contributor.funderKU Leuvenen
dc.contributor.funderNational Institutes of Healthen
dc.contributor.funderScience Foundation Irelanden
dc.date.accessioned2019-05-02T15:35:21Z
dc.date.available2019-05-02T15:35:21Z
dc.date.issued2019-01-16
dc.date.updated2019-05-02T15:18:56Z
dc.description.abstractAcyclic nucleoside phosphonates represent a well-defined class of clinically used nucleoside analogs. All acyclic nucleoside phosphonates need intracellular phosphorylation before they can bind viral DNA polymerases. Recently, a novel class of alpha-carboxynucleoside phosphonates have been designed to mimic the natural 2′-deoxynucleotide 5′-triphosphate substrates of DNA polymerases. They contain a carboxyl group in the phosphonate moiety linked to the nucleobase through a cyclic or acyclic bridge. Alpha-carboxynucleoside phosphonates act as viral DNA polymerase inhibitors without any prior requirement of metabolic conversion. Selective inhibitory activity against retroviral reverse transcriptase and herpesvirus DNA polymerases have been demonstrated. These compounds have a unique mechanism of inhibition of viral DNA polymerases, and provide possibilities for further modifications to optimize and fine tune their antiviral DNA polymerase spectrum.en
dc.description.sponsorshipKU Leuven (Grants PF 10/018 and GOA 10/14); National Institutes of Health (Grant P50 GM103368 and Grant R37 AI027690 MERIT Award);en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationBalzarini, J., Ford, A., Maguire, N. M., John, J., Das, K., Arnold, E., Dehaen, W. and Maguire, A. (2019) 'Alpha-carboxynucleoside phosphonates: direct-acting inhibitors of viral DNA polymerases', Future Medicinal Chemistry, 11(2), pp. 137-154. doi: 10.4155/fmc-2018-0324en
dc.identifier.doi10.4155/fmc-2018-0324en
dc.identifier.endpage154en
dc.identifier.issn1756-8919
dc.identifier.issn1756-8927
dc.identifier.issued2en
dc.identifier.journaltitleFuture Medicinal Chemistryen
dc.identifier.startpage137en
dc.identifier.urihttps://hdl.handle.net/10468/7845
dc.identifier.volume11en
dc.language.isoenen
dc.publisherFuture Scienceen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Technology and Innovation Development Award (TIDA)/05/PICA/B802 TIDA 09/IE/Powder diffraction of pharmaceutical co-crystals/en
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Technology and Innovation Development Award (TIDA)/14/TIDA/2402/IE/Synthesis and biological evaluation of prodrug derivatives of _-carboxynucleosidephosphonate NRTIs (_ -CNPs)/en
dc.relation.urihttps://www.future-science.com/doi/abs/10.4155/fmc-2018-0324
dc.rights© 2019 Future Science Groupen
dc.subjecta-carboxynucleoside phosphonate (a-CNP)en
dc.subjectAcyclic nucleoside phosphonate (ANP)en
dc.subjectChemotherapeuticsen
dc.subjectHerpes virusesen
dc.subjectHIVen
dc.subjectNucleoside-analog inhibitoren
dc.subjectReverse transcriptase (RT)en
dc.subjectViral DNA polymeraseen
dc.titleAlpha-carboxynucleoside phosphonates: direct-acting inhibitors of viral DNA polymerasesen
dc.typeArticle (peer-reviewed)en
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