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Improved thrombin binding aptamer by incorporation of a single unlocked nucleic acid monomer
Nucleic Acid Center, Department of Physics and Chemistry, University of of Southern Denmark, 5230 Odense M, Denmark.
Nucleic Acid Center, Department of Biochemistry and Molecular Biology, University of of Southern Denmark, Campusvej 55, Odense M 5230, Denmark.
Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, University of of Southern Denmark, Sdr. Boulevard, 5000 Odense C, Denmark.
Nucleic Acid Center, Department of Biochemistry and Molecular Biology, University of of Southern Denmark, Campusvej 55, Odense M 5230, Denmark.
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2011 (English)In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 39, no 3, 1155-1164 p.Article in journal (Refereed) Published
Abstract [en]

A 15-mer DNA aptamer (named TBA) adopts a G-quadruplex structure that strongly inhibits fibrin-clot formation by binding to thrombin. We have performed thermodynamic analysis, binding affinity and biological activity studies of TBA variants modified by unlocked nucleic acid (UNA) monomers. UNA-U placed in position U3, U7 or U12 increases the thermodynamic stability of TBA by 0.15-0.50kcal/mol. In contrast, modification of any position within the two G-quartet structural elements is unfavorable for quadruplex formation. The intramolecular folding of the quadruplexes is confirmed by Tm versus ln c analysis. Moreover, circular dichroism and thermal difference spectra of the modified TBAs displaying high thermodynamic stability show bands that are characteristic for antiparallel quadruplex formation. Surface plasmon resonance studies of the binding of the UNA-modified TBAs to thrombin show that a UNA monomer is allowed in many positions of the aptamer without significantly changing the thrombin-binding properties. The biological effect of a selection of the modified aptamers was tested by a thrombin time assay and showed that most of the UNA-modified TBAs possess anticoagulant properties, and that the construct with a UNA-U monomer in position 7 is a highly potent inhibitor of fibrin-clot formation. © 2010 The Author(s).

Place, publisher, year, edition, pages
Oxford University Press, 2011. Vol. 39, no 3, 1155-1164 p.
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Biochemistry and Molecular Biology
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URN: urn:nbn:se:liu:diva-143341DOI: 10.1093/nar/gkq823ISI: 000287257500039PubMedID: 20870750Scopus ID: 2-s2.0-79951575374OAI: oai:DiVA.org:liu-143341DiVA: diva2:1162514
Available from: 2017-12-04 Created: 2017-12-04 Last updated: 2017-12-13Bibliographically approved

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Hernandez, Frank J

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