dc.contributor.author | Mikalkėnas, Algirdas | |
dc.contributor.author | Ravoitytė, Bazilė | |
dc.contributor.author | Tauraitė, Daiva | |
dc.contributor.author | Servienė, Elena | |
dc.contributor.author | Meškys, Rolandas | |
dc.contributor.author | Serva, Saulius | |
dc.date.accessioned | 2023-09-18T17:06:39Z | |
dc.date.available | 2023-09-18T17:06:39Z | |
dc.date.issued | 2018 | |
dc.identifier.issn | 1475-6366 | |
dc.identifier.uri | https://etalpykla.vilniustech.lt/handle/123456789/119735 | |
dc.description.abstract | Small molecule inhibitors have a powerful blocking action on viral polymerases. The bioavailability of the inhibitor, nevertheless, often raise a significant selectivity constraint and may substantially limit the efficacy of therapy. Phosphonoacetic acid has long been known to possess a restricted potential to block DNA biosynthesis. In order to achieve a better affinity, this compound has been linked with natural nucleotide at different positions. The structural context of the resulted conjugates has been found to be crucial for the acquisition by DNA polymerases. We show that nucleobase-conjugated phosphonoacetic acid is being accepted, but this alters the processivity of DNA polymerases. The data presented here not only provide a mechanistic rationale for a switch in the mode of DNA synthesis, but also highlight the nucleobase-targeted nucleotide functionalization as a route for enhancing the specificity of small molecule inhibitors. | eng |
dc.format | PDF | |
dc.format.extent | p. 384-389 | |
dc.format.medium | tekstas / txt | |
dc.language.iso | eng | |
dc.relation.isreferencedby | Scopus | |
dc.relation.isreferencedby | DOAJ | |
dc.relation.isreferencedby | Chemical abstracts | |
dc.relation.isreferencedby | BIOSIS Previews | |
dc.relation.isreferencedby | SciSearch | |
dc.relation.isreferencedby | Science Citation Index Expanded (Web of Science) | |
dc.source.uri | https://doi.org/10.1080/14756366.2017.1417275 | |
dc.subject | FM01 - Biokatalitinių procesų modeliavimas / Modelling of biocatalytic processes | |
dc.title | Conjugation of phosphonoacetic acid to nucleobase promotes a mechanism-based inhibition | |
dc.type | Straipsnis Web of Science DB / Article in Web of Science DB | |
dcterms.references | 24 | |
dc.type.pubtype | S1 - Straipsnis Web of Science DB / Web of Science DB article | |
dc.contributor.institution | Vilniaus universitetas | |
dc.contributor.institution | Vilniaus universitetas Gamtos tyrimų centras | |
dc.contributor.institution | Vilniaus Gedimino technikos universitetas Vilniaus universitetas | |
dc.contributor.institution | Vilniaus Gedimino technikos universitetas Gamtos tyrimų centras | |
dc.contributor.faculty | Fundamentinių mokslų fakultetas / Faculty of Fundamental Sciences | |
dc.subject.researchfield | N 004 - Biochemija / Biochemistry | |
dc.subject.researchfield | N 010 - Biologija / Biology | |
dc.subject.researchfield | T 005 - Chemijos inžinerija / Chemical engineering | |
dc.subject.ltspecializations | L105 - Sveikatos technologijos ir biotechnologijos / Health technologies and biotechnologies | |
dc.subject.en | HIV-1 reverse transcriptase | |
dc.subject.en | M.MuLV | |
dc.subject.en | Klenow exo- | |
dc.subject.en | Inhibition | |
dc.subject.en | Distributive mechanism | |
dcterms.sourcetitle | Journal of enzyme inhibition and medicinal chemistry | |
dc.description.issue | no. 1 | |
dc.description.volume | Vol. 33 | |
dc.publisher.name | Informa | |
dc.publisher.city | London | |
dc.identifier.doi | 000423686000001 | |
dc.identifier.doi | 2-s2.0-85041840484 | |
dc.identifier.doi | 10.1080/14756366.2017.1417275 | |
dc.identifier.elaba | 26438933 | |