A structure-activity relationship of a thrombin-binding aptamer containing LNA in novel sites
| Autor: | Chen Jianshu, Yu Yi, Wang Xudong, Zhang Yanlu, Guoqing Ying, ZhiMing Ou, XingRu Lu, Jianfeng Mei |
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| Rok vydání: | 2019 |
| Předmět: |
Molecular model
Aptamer Clinical Biochemistry Oligonucleotides Pharmaceutical Science Molecular Dynamics Simulation 01 natural sciences Biochemistry chemistry.chemical_compound Structure-Activity Relationship Thrombin Drug Discovery medicine Structure–activity relationship Nucleotide Locked nucleic acid Molecular Biology chemistry.chemical_classification 010405 organic chemistry Organic Chemistry Aptamers Nucleotide Combinatorial chemistry 0104 chemical sciences Thymine 010404 medicinal & biomolecular chemistry Electrophoresis chemistry Molecular Medicine medicine.drug |
| Zdroj: | Bioorganicmedicinal chemistry. 27(14) |
| ISSN: | 1464-3391 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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