Stabilization of novel immunoglobulin switch regions G-quadruplexes by naphthalene and quinoline-based ligands
Josue Carvalho, João Ferreira, P. Pereira, E. Coutinho, Aurore Guédin, Pierre Nottelet, Gilmar F. Salgado, Jean-Louis Mergny, J.A. Queiroza, F. Sousa, Eurico J. Cabrita, C. Cruz
The topological study of novel quadruplex-forming DNA sequences found in immunoglobulin switch regions Sμ and Sγ3 is described along with the synthesis and characterization of naphthalene and quinoline-based ligands for the G-quadruplex binding and stabilization. Several biophysical and biochemical techniques are employed to assess the G-quadruplex formation and stabilization by the ligands. The results indicate that 58Sγ3 folds into a parallel-stranded G-quadruplex structure in K+ buffer while 33Sμ folds into a hybrid-type G-quadruplex in the same buffer. The novel naphthalene and quinoline-based ligands bind and stabilize specifically a variety of G-quadruplexes. This study provides evidence of the importance of G-quadruplex structures to the biology of immunoglobulin class switch recombination.
Circular dichroism, Ligand binding, Protein folding, Biochemistry