Stability Is Not Everything: The Case of the Cyclisation of a Thrombin-Binding Aptamer

Abstract

With the aim of developing a new approach to obtain improved aptamers, a cyclic thrombin-binding aptamer (TBA) analogue (cycTBA) has been prepared by exploiting a copper(I)-assisted azide-alkyne cycloaddition. The markedly increased serum resistance and exceptional thermal stability of the G-quadruplex versus TBA were associated with halved thrombin inhibition, which suggested that some flexibility in the TBA structure was necessary for protein recognition.

Keywords: G-quadruplexes; aptamers; click chemistry; cyclization; molecular recognition.