Aiming to improve binding of porphyrin diphenyl guanidinium conjugates to guanine-quadruplexes: When size matters.

Aiming to improve the binding to Guanine quadruplexes of different topologies, docking studies of porphyrin diphenyl guanidine conjugates previously prepared with an O or a S bridge between the diphenyl moiety and a newly design derivative with an SO2 bridge were carried out using different guanine quadruplexes of different topologies (four parallel, one antiparallel and one hybrid). Positive results were obtained from these computational studies drove us to prepare the SO2 bridge conjugate improving the synthetic route previously reported by us. Biophysical experiments such as UV-thermal melting and circular dichroism indicated the lack of binding to the double stranded DNA and poor binding of the new derivative prepared to any of the guanine quadruplexes studied. These results show that the size of this SO2 bridge could be responsible of the poor experimental binding to guanine quadruplexes.

Dual-binding conjugates of diaromatic guanidines and porphyrins for recognition of G-quadruplexes.

The first conceptualised class of dual-binding guanine quadruplex binders has been designed, synthesised and biophysically studied. These compounds combine diaromatic guanidinium systems and neutral tetra-phenylporphyrins (classical binding moiety for guanine quadruplexes) by means of a semi-rigid linker. An extensive screening of a variety of guanine quadruplex structures and double stranded DNA via UV-vis, FRET and CD experiments revealed the preference of the conjugates towards guanine quadruplexes. Additionally, docking studies indicate the potential dual mode of binding.