Zn Ions Change Binding Mode of TOEPyP4 with DNA and Cause DNA Transition from B to C and Zn-Like Conformations

Abstract

It is known that at low concentrations of TMPyP4, this porphyrin predominantly intercalates between GC pairs at GC-rich sites of duplex DNA and G-quadruplexes of various constructions, and stabilizes these structures. However, there are still some arguable suggestions about the exact binding sites and modes of TMPyP4 to GC-rich regions of DNA in case of helation of divalent ions with help of the porphrin, which makes porphyrin structure asymmetric. We examined TOEPyP4-analogue of TMPyP4-and studied interaction of TOEPyP4 into the calf thymus DNA at presence of nanomole concentrations of one of the most important microelements in cell vital function-Zn ion. On the basis of CD and absorption spectra of the DNA-TOEPyP4 mixture, it was determined that nanomole concentrations of Zn ions changed porphyrin intercalative binding mode to some external binding modes, which initiated transition of the canonic B conformation of DNA into C-like conformation, and incubation of the (DNA-TOEP4) + Zn mixture at 37˚C caused B-Z-like transition, but no transition was observed for the DNA-TOEPyP4 mixture. In particular, at 10 mM·NaCl, TOEPyP4/DNA = 0.02, the binding mode change was observed in the concentration range from 150 to 300 nM·Zn, and the B-C-like transition occurred from 150 to 600 nM·Zn. The B-Z transition at TOEPyP4/DNA = 0.015, Zn/DNA = 0.015, NaCI 10 mM, T = 37˚C was observed within incubation time interval from 0.3 to 20 hours, and maximal percents of Z-like form was seen when incubation time interval was from 5 to 6 hours.

Binding of Metallated Porphyrin-Imidazophenazine Conjugate to Tetramolecular Quadruplex Formed by Poly(G): a Spectroscopic Investigation

“…4). This assumption agrees well with data of Kelly and Murphy [53] showing that ZnTMPyP4 does not intercalate into DNA, as well as with the results obtained by Monaselidze et al [54], revealing that metallization of the similar porphyrin by Zn 2+ ions changes the mode of its binding to DNA from intercalation to groove binding. In our case, metallization of porphyrin part of conjugate also leads to a change in the type of the conjugate binding to four-stranded poly(G) as compared with data described in Ref.…”