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

Abstract

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.

Keywords: Diphenyl guanidines; Docking; Guanine-quadruplexes; UV thermal melting.