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Investigating the properties of TBA variants with twin thrombin binding domains
Teresa Amato1, Antonella Virgilio1, Luciano Pirone2
1Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, 80131, Napoli, Italy.
Abstract:
In this paper, we report studies concerning thrombin binding aptamer (TBA) dimeric derivatives in which the 3'-ends of two TBA sequences have been joined by means of linkers containing adenosine or thymidine residues and/or a glycerol moiety. CD and electrophoretic investigations indicate that all modified aptamers are able to form G-quadruplex domains resembling that of the parent TBA structure. However, isothermal titration calorimetry measurements of the aptamer/thrombin interaction point to different affinities to the target protein, depending on the type of linker. Consistently, the best ligands for thrombin show anticoagulant activities higher than TBA. Interestingly, two dimeric aptamers with the most promising properties also show far higher resistances in biological environment than TBA.
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