Favorable 2'-substitution in the loop region of a thrombin-binding DNA aptamer

Bioorg Med Chem Lett. 2018 Jun 1;28(10):1765-1768. doi: 10.1016/j.bmcl.2018.04.027. Epub 2018 Apr 13.

Abstract

Simple 2'-OMe-chemical modification in the loop region of the 15mer G-rich DNA sequence GGTTGGTGTGGTTGG is reported. The G-quadruplex structure of this thrombin-binding aptamer (TBA), is stabilized by single modifications (T → 2'-OMe-U), depending on the position of the modification. The structural stability also renders significantly increased inhibition of thrombin-induced fibrin polymerization, a process closely associated with blood-clotting.

Keywords: 2′-O-methyl ribo-uridine; Fibrin polymerization; G-quadruplex; Thrombin binding aptamer; Thrombin time.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aptamers, Nucleotide / chemistry
  • Aptamers, Nucleotide / pharmacology*
  • Binding Sites
  • Blood Coagulation / drug effects
  • Dose-Response Relationship, Drug
  • Fibrin / antagonists & inhibitors
  • Fibrin / metabolism
  • G-Quadruplexes
  • Molecular Structure
  • Polymerization / drug effects
  • Structure-Activity Relationship
  • Thrombin / antagonists & inhibitors*

Substances

  • Aptamers, Nucleotide
  • thrombin aptamer
  • Fibrin
  • Thrombin