Expanding the recognition interface of the thrombin-binding aptamer HD1 through modification of residues T3 and T12.

ABSTRACT: Post-SELEX modification of DNA aptamers is an established strategy to improve their affinity or inhibitory characteristics. In this study, we examined the possibility of increasing the recognition interface between the thrombin-binding aptamer HD1 (TBA) and thrombin by adding a chemically modified side chain to selected nucleotide residues. A panel of 22 TBA variants with N3-modified residues T3 and T12 was prepared by a two-step modification procedure. Aptamers were characterized by a combination of biophysical and biochemical methods. We identified mutants with enhanced affinity and improved anticoagulant activity. The crystal structures of thrombin complexes with three selected modified variants revealed that the modified pyrimidine base invariably allocates in proximity to thrombin res

SUBMITTER: Smirnov I 

PROVIDER: S-EPMC7868722 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature