Putative Mechanisms Underlying High Inhibitory Activities of Bimodular DNA Aptamers to Thrombin
AbstractNucleic acid aptamers are prospective molecular recognizing elements. Similar to antibodies, aptamers are capable of providing specific recognition due to their spatial structure. However, the apparent simplicity of oligonucleotide folding is often elusive, as there is a balance between several conformations and, in some cases, oligomeric structures. This research is focused on establishing a thermodynamic background and the conformational heterogeneity of aptamers taking a series of thrombin DNA aptamers having G-quadruplex and duplex modules as an example. A series of aptamers with similar modular structures was characterized with spectroscopic and chromatographic techniques, providing examples of the conformational homogeneity of aptamers with high inhibitory activity, as well as a mixture of monomeric and oligomeric species for aptamers with low inhibitory activity. Thermodynamic parameters for aptamer unfolding were calculated, and their correlation with aptamer functional activity was found. Detailed analysis of thrombin complexes with G-quadruplex aptamers bound to exosite I revealed the similarity of the interfaces of aptamers with drastically different affinities to thrombin. It could be suggested that there are some events during complex formation that have a larger impact on the affinity than the states of initial and final macromolecules. Possible mechanisms of the complex formation and a role of the duplex module in the association process are discussed. View Full-Text
- Supplementary File 1:
PDF-Document (PDF, 1216 KB)
Share & Cite This Article
Zavyalova, E.G.; Legatova, V.A.; Alieva, R.S.; Zalevsky, A.O.; Tashlitsky, V.N.; Arutyunyan, A.M.; Kopylov, A.M. Putative Mechanisms Underlying High Inhibitory Activities of Bimodular DNA Aptamers to Thrombin. Biomolecules 2019, 9, 41.
Zavyalova EG, Legatova VA, Alieva RS, Zalevsky AO, Tashlitsky VN, Arutyunyan AM, Kopylov AM. Putative Mechanisms Underlying High Inhibitory Activities of Bimodular DNA Aptamers to Thrombin. Biomolecules. 2019; 9(2):41.Chicago/Turabian Style
Zavyalova, Elena G.; Legatova, Valeriia A.; Alieva, Rugiya S.; Zalevsky, Arthur O.; Tashlitsky, Vadim N.; Arutyunyan, Alexander M.; Kopylov, Alexey M. 2019. "Putative Mechanisms Underlying High Inhibitory Activities of Bimodular DNA Aptamers to Thrombin." Biomolecules 9, no. 2: 41.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.