Binding Interactions of Zinc Cationic Porphyrin with Duplex DNA: From B-DNA to Z-DNA.

Tingxiao Qin,Kunhui Liu,Di Song,Hongmei Su,Chunfan Yang,Hongmei Zhao

doi:10.3390/ijms19041071

Abstract

Recognition of unusual left-handed Z-DNA by specific binding of small molecules is crucial for understanding biological functions in which this particular structure participates. Recent investigations indicate that zinc cationic porphyrin (ZnTMPyP4) is promising as a probe for recognizing Z-DNA due to its characteristic chiroptical properties upon binding with Z-DNA. However, binding mechanisms of the ZnTMPyP4/Z-DNA complex remain unclear. By employing time-resolved UV-visible absorption spectroscopy in conjunction with induced circular dichroism (ICD), UV-vis, and fluorescence measurements, we examined the binding interactions of ZnTMPyP4 towards B-DNA and Z-DNA. For the ZnTMPyP4/Z-DNA complex, two coexisting binding modes were identified as the electrostatic interaction between pyridyl groups and phosphate backbones, and the major groove binding by zinc(II) coordinating with the exposed guanine N7. The respective contribution of each mode is assessed, allowing a complete scenario of binding modes revealed for the ZnTMPyP4/Z-DNA. These interaction modes are quite different from those (intercalation and partial intercalation modes) for the ZnTMPyP4/B-DNA complex, thereby resulting in explicit differentiation between B-DNA and Z-DNA. Additionally, the binding interactions of planar TMPyP4 to DNA were also investigated as a comparison. It is shown that without available virtual orbitals to coordinate, TMPyP4 binds with Z-DNA solely in the intercalation mode, as with B-DNA, and the intercalation results in a structural transition from Z-DNA to B-ZNA. These results provide mechanistic insights for understanding ZnTMPyP4 as a probe of recognizing Z-DNA and afford a possible strategy for designing new porphyrin derivatives with available virtual orbitals for the discrimination of B-DNA and Z-DNA.

Highlights

DNA molecules are highly polymorphic and can form multiple conformations under different physiological conditions [1,2]
Identical hypochromicity and bathochromic shift, similar negative induced circular dichroism (ICD) bands at 436 nm and fluorescence quenching appear in the absorption, ICD and fluorescence spectra of TMPyP4 (Figure 2b, Figure 3b and Figure S1b) when B-DNA is replaced by Z-DNA
We comprehensively studied the binding interactions of ZnTMPyP4 with two different duplex DNA, B-DNA and Z-DNA, by combining transient UV-vis absorption spectroscopy with steady-state measurements (UV-vis, fluorescence, and ICD)

Summary

Introduction

DNA molecules are highly polymorphic and can form multiple conformations under different physiological conditions [1,2]. The most common structure of DNA is known as B-DNA, a right-handed double helix with the negatively charged deoxyribose-phosphate backbone outside and stacked base pairs inside. E.g., high ionic strengths, in the presence of highly charged cations or some small molecules, certain B-DNA sequences can transform to left-handed helical conformations called Z-DNA with the zig-zag backbone and the stacked base pairs partially exposed to the outside [2,3,4]. A large number of small molecules such as porphyrin molecules and its analogues, have been reported to bind with B-DNA and Z-DNA, only a few of them can recognize Z-DNA via detection of particular binding modes with Z-DNA [9,10,11,12]. This indicates that selecting an appropriate small molecule as a probe for Z-DNA requires a deep mechanistic understanding for the binding modes of small molecules to B-DNA and Z-DNA

Methods

Results

Conclusion