The RNA-binding And RNA Stability Studies Of Regulation By Chemical Small Molecules

DNA is material base of the genetic information that in process of storage, transfer and expression, and its structure corresponds to his function, and It was closely associated with cancer and anticancer. RNA, however, participating in proteins assembly, and playing a key role in gene regulation process, its structure is associated with the diagnosis and treatment of some diseases. Therefore, according to difference of RNA structure to regulate gene expression. Due to two opposite polarity exists in the double helix chain in the big groove excess hydrogen bond donors and receptors, and these helical structure the outside of the hydrogen bond donor and receptor could combination to the third chain by specificity to formed triplex helix structure. So, a variety of RNA structure could be formed to accord to conjugate the different types of base-pairs. But triplex helix RNA is not normal existence state of RNA, and its stability and conformation are susceptible to change by the influence of environment. Therefore, the triple helix RNA stability and conformational conversion regulation that is the premise of its application in gene therapy. In this paper, constructing contain uracil structure function ruthenium polypyridine complexes by the molecular structure design, and characterized in detail by elemental analysis, MS and NMR; The triple, double and single stranded RNA binding interaction mechanism of these complexes have studied with ultraviolet spectrum, fluorescence spectrum, the steady-state fluorescence quenching study, viscosity, the thermal denaturation and circular dichroism spectrum. At the same time, binding aromatic small molecules with triplex, duplex and single stranded RNA that probing into both of functional mechanism and conformation transition. The above research work on exploring the structure of aromatic small molecules and metal complexes dinding to different structure nucleic acid of mechanism that It has important research significance for biological macromolecules in stereoselectivity by specific recognition. This thesis mainly consists of four chapters, the details are as follows:In the first chapter, to illustrate the produce and development of bioinorganic chemistry and different structure and composition of nucleic acid, and the theoretical basis and medical applications for binding aromatic small molecules and metal complexes with nucleic acid.In the second chapter, building complexes Ru1, Ru2 and interact with triple helix RNA, the result proves that complexes Ru1 and Ru2 combined with triple helix RNA through intercalative interaction and observed by spectroscopy, thermodynamics etc. It would be generate strong π-π stacking between the base pairs, and made the third chain has good stabilization that the unwinding temperature increased by 8.1 oC and 12.9 oC, respectively. Meanwhile, its conformation to have certain regulation effect.In the third chapter, to detail studies of the complexes Ru1 and Ru2 bonding with double helix RNA through spectroscopy, thermodynamics and viscosity means etc. The results show that the two complexes combined with the double helix RNA by intercalative interaction and the affinity of the bond is greater than the affinity which complexes bonding to triple helix RNA.In the fourth chapter, the aromatic small molecule methylene blue(MB) interact with triplex, duplex and single stranded RNA, spectroscopy, thermodynamics and viscosity test method is used to study the mode and mechanism of the linkage between the two. the results showed that MB is through a variety of bonding model to the role of RNA, under the low concentration ratio, insertion combined with compete with electrostatic effect relationship; But in the high concentration ratio, electrostatic interactions is the major factor.