G-quadruplexes in telomeric repeats are conserved in a solvent-free environment

The structural properties of G-quadruplex forming sequences. such as the human telomeric repeat d(T(2)AG(3))(n), are of great interest due to their role in cancer and cellular aging. To determine if G-quadruplexes are present in a solvent-free environment. different lengths of the telomeric repeat d(T(2)AG(3))(n) (where n = 1, 2, 4 and 6) and dTG(4)T were investigated with mass specteometry, ion mobility and molecular dynamics calculations. Nano-ESI-MS illustrated quadruples stoichiometries compatible with G-quadruplex Structure.; for each sequence, with dT(2)AG(3) and dTG(4)T forming 4-strand complexes with two and three NH4+ adducts. d(T(2)AG(3))(2) a 2-strand complex. and d(T(2)AG(3))(4) and d(T(2)AG(3))(6) remaining single-stranded. Experimental cross sections were obtained for all species using ion mobility method.,. In all case.,. these could be quantitatively matched to model cross sections with specific strand orientations (parallel/antiparallel) and structures. For each species, the solvent-free structures agreed with the solution CD measurements, but the ion mobility/modeling procedure often gave Much more detailed structural information. (C) 2006 Elsevier B.V. All rights reserved.