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

Claudia Riccardi (1) , Albert Meyer (2) , Jean-Jacques Vasseur (2) , Irene Russo krauss , Luigi Paduano (3) , Rosario Oliva , Luigi Petraccone (4) , François Morvan (2) , Daniela Montesarchio (4)

1 CDPC - Centre de Droit Pénal et de Criminologie
2 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]
3 Dipartimento di Scienze Chimiche, Complesso Universitario Monte Sant’Angelo
4 Department of Chemical Sciences

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.

Mots clés: G-quadruplexes; aptamers; click chemistry; cyclization; molecular recognition

Domaines: Chimie; Chimie organique; Chimie thérapeutique; Chimie analytique

Claudia Riccardi, Albert Meyer, Jean-Jacques Vasseur, Irene Russo krauss, Luigi Paduano, et al.. Stability Is Not Everything: The Case of the Cyclisation of a Thrombin‐Binding Aptamer. ChemBioChem, 2019, ⟨10.1002/cbic.201900045⟩. ⟨hal-02197218⟩