Binding properties of pyrene-porphyrin dyad to G-quadruplexes in the presence of K+ and Na+ ion and their effect on stability

Abstract

The binding property of 1-pyrenyl-tris(N-methyl-p-pyridino)porphyrin (a pyrene-porphyrin dyad; Py-TMPyP) to various G-quadruplexes formed from 5′-G3TnG3TGTG3TnG3 (n = 2 and 3, designated as S1 and S2, respectively) and conformation-dependent stability of the Py-TMPyP–quadruplex complexes were investigated via thermal melting profiles and circular dichroism (CD) spectral analyses. Upon binding to parallel (in the presence of K+) and antiparallel (in the presence of Na+) S1 and S2 quadruplexes, a bisignate CD signal in the Soret region was induced for all four G-quadruplexes, indicating that the direction of interaction of the electric transition moments of the porphyrins differed. This suggested that the porphyrin binding site in the G-quadruplex is highly unsymmetric. Py-TMPyP induced a moderately negative CD signal in the pyrene absorption region when binding to the parallel S1 quadruplex and parallel/antiparallel mixed S2 quadruplex. In contrast, a strongly negative CD signal was observed for the Py-TMPyP bound to antiparallel S1 quadruplex, while no CD signal appeared for the antiparallel S2 quadruplex. Considering that two and three thymine bases are present in the loops of S1 and S2, respectively, the number of the thymines in the loop is important for the interaction of pyrene and the G-quadruplex. The thermal melting study showed that the antiparallel form of the G-quadruplex was generally less stable compared to the corresponding parallel conformation. The presence of Py-TMPyP caused destabilization of the G-quadruplexes.