Synthesis, characterization and in vitro activity of thrombin-binding DNA aptamers with triazole internucleotide linkages.
| Autor: | Varizhuk AM; Institute for Physical-Chemical medicine, Malaya Pirogovskaya Str., 1a, Moscow 119435, Russia; Engelhardt Institute of Molecular Biology, Vavilov Str., 32 Moscow 119991, Russia. Electronic address: annavarizhuk@gmail.com., Tsvetkov VB, Tatarinova ON, Kaluzhny DN, Florentiev VL, Timofeev EN, Shchyolkina AK, Borisova OF, Smirnov IP, Grokhovsky SL, Aseychev AV, Pozmogova GE |
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| Jazyk: | angličtina |
| Zdroj: | European journal of medicinal chemistry [Eur J Med Chem] 2013 Sep; Vol. 67, pp. 90-7. Date of Electronic Publication: 2013 Jun 25. |
| DOI: | 10.1016/j.ejmech.2013.06.034 |
| Abstrakt: | A series of DNA aptamers bearing triazole internucleotide linkages that bind to thrombin was synthesized. The novel aptamers are structurally analogous to the well-known thrombin-inhibiting G-quadruplexes TBA15 and TBA31. The secondary structure stability, binding affinity for thrombin and anticoagulant effects of the triazole-modified aptamers were measured. A modification in the central loop of the aptamer quadruplex resulted in increased nuclease resistance and an inhibition efficiency similar to that of TBA15. The likely aptamer-thrombin binding mode was determined by molecular dynamics simulations. Due to their relatively high activity and the increased resistance to nuclease digestion imparted by the triazole internucleotide linkages, the novel aptamers are a promising alternative to known DNA-based anticoagulant agents. (Copyright © 2013 Elsevier Masson SAS. All rights reserved.) |
| Databáze: | MEDLINE |
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