Investigation of formation, recognition, stabilization, and conversion of dimeric G-quadruplexes of HIV-1 integrase inhibitors by Electrospray ionization mass Spectrometry

The dimeric G-quadruplex structures of d(GGGTGGGTGGGTGGGT) (SI) and d(GTGGTGGGTGGGTGGGT) (S2), the potent nanomolar HIV-1 integrase inhibitors, were detected by electrospray ionization mass spectrometry (ESI-MS) for the first time. The formation and conversion of the dimers were induced by NH4+, DNA concentration, pH, and the binding molecules. We directly observed the specific binding of a perylene derivative (TeL03) and hnhnIm beta Dp in one system consisting of the intramolecular and the dimeric G-quadruplexes of the HIV-1 integrase inhibitor, which suggested that Tel03 could shift the equilibrium to the dimeric G-quadruplex formation, while hnImIm beta Dp induces preferentially a structural change from the dimer to the intramolecular G-quadruplex. The results of this study indicated that TeL03 and ImImIm beta Dp favor the stabilizationof the dimeric G-quadruplex structures.