Tetraplex Structure Formation in the Thrombin-Binding DNA Aptamer by Metal Cations Measured by Vibrational Spectroscopy

Abstract

Formation of intramolecular tetraplex structures by the thrombin-binding DNA aptamer (TBA) in the presence of K+, Pb2+, Ba2+, Sr2+ and Mn2+ has been studied by vibrational spectroscopy. All tetraplex structures contain G-G Hoogsteen type base pairing, both C2′endo/anti and C2′endo/syn deoxyguanosine glycosidic conformations and local B like form DNA phosphate geometries. Addition of Pb2+ ions modifies the structure by interacting at the level of the guanine carbonyl groups. The very important downshift of the guanine C6=O6 carbonyl vibration mode in the TBA spectrum induced by the addition of one Pb2+ ion per TBA molecule is in agreement with a localization of the metal ion between both guanine quartets. FTIR melting experiments show an important stabilization of the tetraplex structure upon addition of Pb2+ ions (ΔT = 15 °C). This strong interaction of lead cations may be correlated with a change in the geometry of the cage formed by the two guanine quartets. A similar but weaker effect is observed for barium and strontium cations.