Study On The Binding Of Small Molecules To DNA And DNA Bases As Well As The Effect Of Gold Nanoparticles On The Binding Behavior

The study on the interaction of DNA with small molecules or proteins is an important research field which involves different research area including Chemistry, Biochemistry, Medicine, Molecular Biology and Physics. Many scientists are interested in the binding of small molecules to DNA, oligonuleotide and so on, because it may lead to explain the structure and function of DNA, the interaction of protein to DNA and the mechanism of anticancer pharmacy, besides, it can also afford valuable information to the design of some new anticancer drugs.In this study, initially we have explored the binding of aspirin to ssDNA, dsDNA, and DNA bases by using fluorescence and AFM (Atomic Force Microscopy), the results indicated that aspirin binds to DNA with a groove binding mode, and the interaction of aspirin to dsDNA is much stronger than that with ssDNA.Then, the binding of DTIC to DNA and DNA bases in the absence and presence of Au nanoparticles has been explored in this work by electrochemical study. The results indicate that the binding of purines (adenine and guanine) to DTIC is stronger than that of pyrimidines (thymine and cytosine) in the order of A>G>C>T. Besides, it was observed that the presence of colloidal Au can enhance the probing sensitivity for the interaction between DTIC with DNA bases. In view of these, we have studied the binding affinity of DTIC to some special oligonuceotides. The results illustrate that DTIC could specially interact with some specific DNA sequences.To further explore the relative mechanism, DTIC was immobilized on glassy carbon electrode (GCE) through amine-containing compounds by using electrochemical oxidation. This method allows DTIC to form a monolayer on the surface of GCE. Cyclic voltammetry of the modified electrode in an aqueous solution of 0.1M KCl, 1 mM Fe(CN)6 3- was detected in the absence and presence of different DNA bases. The results show that the specific interactions of DTIC with different DNA bases may dramatically change the important interfacial characteristic of the surface (such as defect density, etc.), which could be utilized as a new probe for the DNA base detection and suggests its potential application as a sensitive coating for some important biological sensing process.Finally, we have explored to utilize DTIC as a DNA molecular probe to sensitively detect specific DNA sequence and single-base mismatch or the single base mutations. We have designed three specific DNA sequence, one of them contains a HS- group, which was immobilized on gold nanoparticles through Au-S bond, while the others were immobilized on GCE through the linkage of Chitosan. The results of electrochemical study indicate that with the effect of gold nanoparticles, DTIC could sensitively detect the single base mismatch of the DNA sequence, and gold nanoparticles can significantly improve its detection sensitivity.