5-Hydroxymethyl-2'-deoxyuridine residues in the thrombin binding aptamer: investigating anticoagulant activity by making a tiny chemical modification.
Chembiochem
; 15(16): 2427-34, 2014 Nov 03.
Article
en En
| MEDLINE
| ID: mdl-25214456
ABSTRACT
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 H9, which showed a marked increase in melting temperature. Although all TBA analogues showed decreased affinities to thrombin, H3, H7, and H9 proved to have improved anticoagulant activities. Our data open up the possibility to enhance TBA biological properties, simply by introducing small chemical modifications.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Timidina
/
Trombina
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Aptámeros de Nucleótidos
/
Anticoagulantes
Tipo de estudio:
Prognostic_studies
Idioma:
En
Año:
2014
Tipo del documento:
Article