Molecular Interactions Between The Anti-cancer Drug Of Oxaliplatin And DNA Studied By Atomic Force Microscope

Platinum anticancer drugs are the first choice for many types of cancer drugs treatments, and its anti-cancer mechanism has been a research focus. DNA is a very important organism biological macromolecules, which participates in the composition of genetic instructions to guide the biological development and the operation of vital functions. High mobility proteins are involved in DNA replication, DNA recombination, gene transcription, chromatin remodeling and other life activities. A large number of literature showedthat the targets of the platinum anticancer drugs is a DNA molecule.Through the study of the interaction between platinum drugs and DNA-high mobility proteins, it is possible to provide a theoretical basis onthe synthesis of new effective platinum anticancer drugs.1. Study of oxaliplatin interact with DNA process using UV spectrometry The interaction of small molecule drug can cause changes in the structure and chemical properties of DNA, through these changes and their mode of action can presumably clarify the mechanism. And the change in position of the absorption peak and absorbance change determine the mode of action of DNA and small molecules by UV absorption spectrum. This method can analyze the interaction ofDNA and oxaliplatin, DNA interaction with the absorption peaks occur after oxaliplatin significant effect redshift and enriched by experiment that took place Mingaoshali platinum and DNA intercalation, accompanied by electrostatic interactions.2. Use of an atomic force microscope to directly observe high resolution molecular structure at different concentrations of oxaliplatin and long-chain linear DNA, circular plasmid and atdifferent time after the formation of a short single-stranded oligonucleotides in the gas phase, according to Structure Data Analysis speculated mechanism oxaliplatin containing target DNA molecule. With the growth duration of action, PUC19 gradually transformed from extending structure into a cyclic structure closer chain crosslinked structure having a plurality of nodes, ultimately transformed into highly compact globular DNA aggregation structure. PUC19DNA chain fragment (1775bp) increased the height of the molecular structure of DNAat the same time conditions with oxaliplatin concentration. The height ofλDNA structural increased and eventually formed aggregation structure. Short oligonucleotides (AG) 5 and G10DNA did not act with oxaliplatin, assembled at the graphite surface parallel orderly pattern, and gradually form a mesh structure and spherical assembly after effect. This is mainly due to the hydrolysis of oxaliplatin active platinum cations with DNA molecules together with purine base-addition, the performance of this process are the concentration and time dependency. Height changes can be attributed to the structure of DNA inter-strand DNA bases with platinum cations formed in the cross-linked and cross-linked structure due to share rooms. These cross-linked structure can occur helicase DNA chain and bent to form a variety of ultra-helix structure, and node structure leaving the height increases. With the large number of active platinum cation adduct to the DNA sequence, it can lead to electrostatic repulsion between DNA strands becomes small, plus oxaliplatin carried ligand cyclohexanedicarboxylic ammonia brought hydrophobic interaction, resulting in DNA Molecular aggregation of spherical structure.3. Use of high-resolution atomic force microscopy to observe the structure of the high mobility of the protein and the formation of DNA and oxaliplatin. HMGB1 a protein high mobility is a potential target for platinum anticancer drugs, which plays a role in the process of platinum anticancer drugs and the role of DNA. From experimental results that a DNA strand appeared a big junction HMGB1 and its height is similar tothe height of DNA, it suggested that HMGB1 may be combined with oxaliplatin-DNA purified by electrostatic attraction together. In this paper, the results in Table interaction occurs between Mingaoshali platinum and DNA, and combined with HMGB1, the experimental results can provide a theoretical basis for the synthesis of new and effective platinum anticancer drugs.