5‐Hydroxymethyl‐2′‐Deoxyuridine Residues in the Thrombin Binding Aptamer: Investigating Anticoagulant Activity by Making a Tiny Chemical Modification

• DOI: 10.1002/cbic.201402355
• Publication Date: 2014-09-11T21:48:16Z
• Authors: Antonella Virgilio; Luigi Petraccone; Maria Scuotto; Valentina Vellecco; Mariarosaria Bucci; Luciano Mayol; Michela Varra; Veronica Esposito; Aldo Galeone
• Keywords: Aptamer; Deoxyuridine; Hydroxymethyl; Residue (chemistry)

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