dc.contributor.author | Kotkowiak, W | |
dc.contributor.author | Wengel, J | |
dc.contributor.author | Scotton, CJ | |
dc.contributor.author | Pasternak, A | |
dc.date.accessioned | 2019-03-06T15:28:25Z | |
dc.date.issued | 2019-02-08 | |
dc.description.abstract | RE31 is a 31-nt DNA aptamer, consisting of the G-quadruplex and a duplex domain, which is able to effectively prolong thrombin time. This article reports on the influence of certain modified nucleotide residues on thermodynamic and biological properties as well as the folding topology of RE31. Particularly, the effect of the presence of nucleosides in unlocked nucleic acid (UNA), locked nucleic acid (LNA), or β-l-RNA series was evaluated. The studies presented herein show that all modified residues can influence thermal and biological stabilities of G-quadruplex in a position-dependent manner. The aptamers modified simultaneously with UNA at the T15 position and LNAs in the duplex part possess the highest value of melting temperature and a 2-fold higher anticoagulant effect. Importantly, RE31 variants modified with nucleosides in UNA, LNA, or β-l-RNA series exhibit unchanged G-quadruplex folding topology. Crucially, introduction of any of the modified residues into RE31 causes prolongation of aptamer stability in human serum. | en_GB |
dc.description.sponsorship | National Science Center | en_GB |
dc.description.sponsorship | Polish Ministry of Science and Higher Education | en_GB |
dc.identifier.citation | Published online 8 February 2019 | en_GB |
dc.identifier.doi | 10.1021/acs.jmedchem.8b01806 | |
dc.identifier.grantnumber | UMO-2015/19/N/NZ5/02246 | en_GB |
dc.identifier.grantnumber | UMO-2013/10/E/ NZ1/00741 | en_GB |
dc.identifier.grantnumber | UMO-2017/25/B/NZ7/00127 | en_GB |
dc.identifier.grantnumber | 27/ SN/2018 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/36328 | |
dc.language.iso | en | en_GB |
dc.publisher | American Chemical Society | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/30735377 | en_GB |
dc.rights.embargoreason | Under embargo until 8 February 2020 in compliance with publisher policy. | |
dc.rights | © 2019 American Chemical Society | en_GB |
dc.subject | G-quadruplex | en_GB |
dc.subject | thrombin | en_GB |
dc.subject | anticoagulants | en_GB |
dc.subject | DNA | en_GB |
dc.subject | aptamer | en_GB |
dc.subject | unlocked nucleic acids | en_GB |
dc.title | Improved RE31 Analogues Containing Modified Nucleic Acid Monomers: Thermodynamic, Structural, and Biological Effects. | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2019-03-06T15:28:25Z | |
dc.identifier.issn | 0022-2623 | |
exeter.place-of-publication | United States | en_GB |
dc.description | This is the author accepted manuscript. The final version is available from the American Chemical Society via the DOI in this record. | en_GB |
dc.identifier.journal | Journal of Medicinal Chemistry | en_GB |
dc.rights.uri | http://www.rioxx.net/licenses/all-rights-reserved | en_GB |
dcterms.dateAccepted | 2019-02-08 | |
rioxxterms.version | AM | en_GB |
rioxxterms.licenseref.startdate | 2019-02-08 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2019-03-06T15:23:54Z | |
refterms.versionFCD | AM | |
refterms.panel | A | en_GB |