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

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dc.contributor.author Balzarini, Jan
dc.contributor.author Ford, Alan
dc.contributor.author Maguire, Nuala M.
dc.contributor.author John, Jubi
dc.contributor.author Das, Kalyan
dc.contributor.author Arnold, Eddy
dc.contributor.author Dehaen, Wim
dc.contributor.author Maguire, Anita R.
dc.date.accessioned 2019-05-02T15:35:21Z
dc.date.available 2019-05-02T15:35:21Z
dc.date.issued 2019-01-16
dc.identifier.citation Balzarini, 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-2018-0324 en
dc.identifier.volume 11 en
dc.identifier.issued 2 en
dc.identifier.startpage 137 en
dc.identifier.endpage 154 en
dc.identifier.issn 1756-8919
dc.identifier.issn 1756-8927
dc.identifier.uri http://hdl.handle.net/10468/7845
dc.identifier.doi 10.4155/fmc-2018-0324 en
dc.description.abstract Acyclic 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.sponsorship KU Leuven (Grants PF 10/018 and GOA 10/14); National Institutes of Health (Grant P50 GM103368 and Grant R37 AI027690 MERIT Award); en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Future Science en
dc.relation.uri https://www.future-science.com/doi/abs/10.4155/fmc-2018-0324
dc.rights © 2019 Future Science Group en
dc.subject a-carboxynucleoside phosphonate (a-CNP) en
dc.subject Acyclic nucleoside phosphonate (ANP) en
dc.subject Chemotherapeutics en
dc.subject Herpes viruses en
dc.subject HIV en
dc.subject Nucleoside-analog inhibitor en
dc.subject Reverse transcriptase (RT) en
dc.subject Viral DNA polymerase en
dc.title Alpha-carboxynucleoside phosphonates: direct-acting inhibitors of viral DNA polymerases en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Alan Ford, Chemistry, University College Cork, Cork, Ireland. +353-21-490-3000 Email: alan.ford@ucc.ie en
dc.internal.availability Full text available en
dc.check.info Access to this article is restricted until 12 months after publication by request of the publisher. en
dc.check.date 2020-01-16
dc.date.updated 2019-05-02T15:18:56Z
dc.description.version Accepted Version en
dc.internal.rssid 483721492
dc.contributor.funder KU Leuven en
dc.contributor.funder National Institutes of Health en
dc.contributor.funder Science Foundation Ireland en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Future Medicinal Chemistry en
dc.internal.copyrightchecked No !!CORA!!
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress alan.ford@ucc.ie en
dc.internal.IRISemailaddress a.maguire@ucc.ie en
dc.relation.project info: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.project info: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


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