AI Article Synopsis
- The report discusses the development of a new modified thrombin-binding aptamer (TBA) that incorporates anti-guanine bases and a loop-locked nucleic acid (LNA) to enhance binding to thrombin.
- Techniques like NMR, circular dichroic spectroscopy, and molecular modeling were used to analyze the three-dimensional structure of two G-quadruplexes formed by the modifications.
- The modifications not only improve the aptamer's stability and affinity for thrombin but also maintain strong inhibitory activity, suggesting that LNA modifications significantly enhance the aptamer's properties.
Article Abstract
In this report, structural characterization, aptamer stability and thrombin of a new modified thrombin-ligand complex binding aptamer (TBA) containing anti-guanine bases and a loop position locked nucleic acid (LNA) are presented. NMR, circular dichroic spectroscopy and molecular modeling were used to characterize the three-dimensional structure of two G-quadruplexes. LNA-modification of the anti-guanosines yields G-quadruplexes that show affinity and inhibitory activity toward thrombin, whereas LNA-modification of a thymine nucleotide in the TGT loop increases the thermal stability of TBA. As assessed by denatured PAGE electrophoresis, all modified aptamers display an increase in environmental stability. The prothrombin time assay and fibrinogen assay showed that the aptamers still had good inhibitory activity, and 15 of them had the longest PT time. Therefore, the LNA modification is well suited to improve the physicochemical and biological properties of the native thrombin-binding aptamer.
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| http://dx.doi.org/10.1016/j.bmc.2019.05.010 | DOI Listing |
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