Thrombin Binding Aptamer, more than a Simple Aptamer: Chemically Modified Derivatives and Biomedical Applications

The thrombin binding aptamer (TBA) is a well characterized chair-like, antiparallel quadruplex structure that binds specifically to thrombin at nanomolar concentrations and therefore it has interesting anticoagulant properties. In this article we review the research involved in the development of new TBA derivatives with improved anticoagulant properties as well as the use of the TBA as a model compound for the study of quadruplex structures. Specifically, we describe the impact of modified nucleosides and non-natural backbones in the guanine tetrads or in the loops and the introduction of pendant groups at the 3' or 5'-ends. The modified oligonucleotides are shown to be excellent tools for the understanding of the molecular structure of the TBA and its folding properties. Finally, we review the use of the TBA-Thrombin recognition system for the development of analytical tools based on the TBA folding.This study was supported by the European Communities (FUNMOL, FP7-NMP- 213382-2), Spanish Ministry of Education (MOL2MED, CTQ2010-20541), the Generalitat de Catalunya (2009/SGR/208), IRB Barcelona, COST (G4net, MP0802) and CIBER-BBN (VI National R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions, Instituto de Salud Carlos III with assistance from the European Regional Development Fund.N