G-quadruplex-based aptamers targeting human thrombin: Discovery, chemical modifications and antithrombotic effects(106 views) Riccardi C, Napolitano E, Platella C, Musumeci D, Montesarchio D
Department of Chemical Sciences, University of Naples Federico II, via Cintia 21, I-80126 Naples, Italy
Department of Advanced Medical and Surgical Sciences, 2(nd) Division of Neurology, Center for Rare Diseases and InterUniversity Center for Research in Neurosciences, University of Campania Luigi Vanvitelli, via Sergio Pansini, 5, I-80131 Naples, Italy. Electronic address: claudia.riccardi@unina.it.
Institute of Biostructures and Bioimages, CNR, via Mezzocannone 16, I-80134 Naples, Italy. Electronic address: domenica.musumeci@unina.it.
References: Not available.
G-quadruplex-based aptamers targeting human thrombin: Discovery, chemical modifications and antithrombotic effects
First studies on thrombin-inhibiting DNA aptamers were reported in 1992, and since then a large number of anticoagulant aptamers has been discovered. TBA - also named HD1, a 15-mer G-quadruplex (G4)-forming oligonucleotide - is the best characterized thrombin binding aptamer, able to specifically recognize the protein exosite I, thus inhibiting the conversion of soluble fibrinogen into insoluble fibrin strands. Unmodified nucleic acid-based aptamers, in general, and TBA in particular, exhibit limited pharmacokinetic properties and are rapidly degraded in vivo by nucleases. In order to improve the biological performance of aptamers, a widely investigated strategy is the introduction of chemical modifications in their backbone at the level of the nucleobases, sugar moieties or phosphodiester linkages. Besides TBA, also other thrombin binding aptamers, able to adopt a well-defined G4 structure, e.g. mixed duplex/quadruplex sequences, as well as homo- and hetero-bivalent constructs, have been identified and optimized. Considering the growing need of new efficient anticoagulant agents associated with the strong therapeutic potential of these thrombin inhibitors, the research on thrombin binding aptamers is still a very hot and intriguing field. Herein, we comprehensively described the state-of-the-art knowledge on the DNA-based aptamers targeting thrombin, especially focusing on the optimized analogues obtained by chemically modifying the oligonucleotide backbone, and their biological performances in therapeutic applications.
G-quadruplex-based aptamers targeting human thrombin: Discovery, chemical modifications and antithrombotic effects