5‐Hydroxymethyl‐2′‐Deoxyuridine Residues in the Thrombin Binding Aptamer: Investigating Anticoagulant Activity by Making a Tiny Chemical Modification. Issue 16 (11th September 2014)

• Record Type: Journal Article
• Authors: Virgilio, Antonella; Petraccone, Luigi; Scuotto, Maria; Vellecco, Valentina; Bucci, Mariarosaria; Mayol, Luciano; Varra, Michela; Esposito, Veronica; Galeone, Aldo
• Is Part Of: Chembiochem. Volume 15:Issue 16(2014)
• Page Start: 2427
• Page End: 2434
• Publication Date: 2014-09-11
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201402355
• Languages: English
• ISSNs: 1439-4227

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>We report an investigation into analogues of the thrombin binding aptamer (TBA). Individual thymidines were replaced by the unusual residue 5‐hydroxymethyl‐2′‐deoxyuridine (hmU). This differs from the canonical thymidine by a hydroxyl group on the 5‐methyl group. NMR and CD data clearly indicate that all TBA derivatives retain the ability to fold into the "chair‐like" quadruplex structure. The presence of the hmU residue does not significantly affect the thermal stability of the modified aptamers compared to the parent, except for analogue <bold>H9</bold>, which showed a marked increase in melting temperature. Although all TBA analogues showed decreased affinities to thrombin, <bold>H3</bold>, <bold>H7</bold>, and <bold>H9</bold> proved to have improved anticoagulant activities. Our data open up the possibility to enhance TBA biological properties, simply by introducing small chemical modifications.</p> </abstract>