A structure-activity relationship of a thrombin-binding aptamer containing LNA in novel sites. Issue 14 (15th July 2019)

• Record Type: Journal Article
• Authors: Ying, GuoQing; Lu, XingRu; Mei, JianFeng; Zhang, YanLu; Chen, JianShu; Wang, XuDong; Ou, ZhiMing; Yi, Yu
• Is Part Of: Bioorganic & medicinal chemistry. Volume 27:Issue 14(2019)
• Page Start: 3201
• Page End: 3207
• Publication Date: 2019-07-15
• Subjects: Aptamer -- Locked nucleic acid -- Oligonucleotides -- TBA -- Anticoagulant activity; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2019.05.010
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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.