Structural Recognition And Reversible Control Of 8-Oxo-Guanine And 5-Formylcytosine Modified Nucleic Acids By Small Molecules

Z-DNA,the left-handed helix DNA,is a secondary structure of DNA.It was first discovered in vitro.With the research progressing,a mass of data confirmed that ZDNA is widely present in chromosomes.In recent years,with the maturity of biotechnology,various biological functions of Z-DNA have been revealed,such as participation in gene regulation,induction of increased genetic instability,induction of autoimmune and apoptosis of the body.Z-DNA has undoubtedly become a new target for the diagnosis,treatment and new drug development of related diseases.The precise control of its structure can help researchers study some important biological processes.Here we have chosen a method that combines the spermine that induces the formation of stable Z-DNA with the action of the host-guest interaction to regulate the B-Z conformational transformation of DNA.We first confirmed the interaction between cucurbituril and spermine by fluorescence spectroscopy.Then we used circular dichroism(CD)and nuclear magnetic resonance(NMR)to monitor the structural changes of DNA.And we proved that CB[7]-driven host-guest competition can achieve the goal of the reversible conversion of B-DNA and Z-DNA.Compared to other methods,our supramolecular host-guest strategy has the advantage of controlling the conversion process of the B/Z configuration without adjusting the p H to alkaline or acidic.Moreover,polyamines are widely distributed in cells.This study provides a new research direction for the reversible and precise regulation of DNA helix structures in vivo.In mammals,5-formylcytosine(5f C)is considered to be an important marker,playing an important role in DNA demethylation and epigenetic regulation,which regulates genes,alters DNA structure,and differentiates cells.It has a close relationship with the disease.Therefore,to target this epigenetic marker and regulate the DNAprotein interactions at this site are important.Supramolecular metal coordination interactions play an important role in the transmission of biological information and have received extensive attention in biological systems.Although there are a large number of metal-peptide complexes,the study of metal-DNA complexes is relatively rare.We have proposed a method of combining metal coordination with DNA containing a 5f C site to achieve the purpose of reversibly regulating the interaction between DNA and protein.We designed and synthesized 2-(aminooxy)-N-(quinolin-8-yl)acetamide(AQA),which is capable of labeling 5f C in DNA selectively.The outer ring hetero atom of 5f C and the aliphatic amine of the auxiliary side arm respectively have affinity for metal ions.And when they are combined,the binding specificity and strength are remarkably enhanced by synergistic action.We studied DNA extension and restriction enzyme digestion at the 5f C site,and regulated the binding of DNA and protein through the coordination of specific metal ions and the decomplexation of chelating agents.The results came from the gel electrophoresis experiments,thermodynamic stability and kinetics experiments.Experiments have shown that metal coordination can reversibly regulate the interaction of DNA and protein at specific sites.This supramolecular-based metal coordination can also be extended to regulate the interaction of other DNA and proteins involved in DNA modification.The host-guest interaction of cucurbituril and the coordination of metals are two important systems of the supramolecular systems.They all take small molecules as the starting point and play an important role in the two regulatory systems we designed.The host-guest interaction provides a potential new direction for the precise and reversible regulation of DNA helix structure,and metal coordination has also been newly developed in the field of DNA epigenetics.