Studies Of Binding Interactions Of Chiral Ruthenium (â…¡) Complexes With G-Quadruplex, And The Influence Of That To Telomerase

G-rich DNA sequences can fold into a four-stranded structures called G-quadruplexes through Hoogsteen hydrogen bond. The formation of G-quadruplex structures can directly inhibite telomerase activity and result dead cancer cell. Human telomere DNA sequences can also form G-quadruplexes. Recent years, the research about anticancer drugs that target G-quadruplexes have become a hot.In my degree thesis,.a series of chiral ruthenium complexes have been synthesized and the research of ruthenium complexes binding to G-quadruplexes have been performed based on previous research achievements. My degree thesis contains four chapters.In chapter 1, the relation between G-quadruplexes and dead cancer cells, the structures of different G-quadruplexes, the G-quadruplex stabilizers and all kinds of methods in the rank of ruthenium complex bind to G-quadruplexes were expounded.In chapter 2, a paire of chiral ruthenium complexes A/A-[Ru(phen)2p-MOPIP]2+(A/A-OMe) and their racemic mixture [Ru(phen)2p-MOPIP]2+(dl-OMe) were synthesized and the activity research were performed by electronic absorption titration, fluorescence spectrum, circular dichroism (CD) and FRET experiments. The UV-Vis and fluorescence spectrum results indicate that two chiral enantiomers may bind to G-quadruplex through intercalative mode. CD spectrum reveals that the chiral enantiomers and the racemic complex can convert the structure of G-quadruplex. FRET experiment show that three complexes all can enhance the Tm value of G-quadruplex, and the binding affility of A-enantiomer is stronger than that ofâ–³-enantiomr.In chapter 3, a paire of chiral ruthenium complexes A/A-[Ru(phen)2p-DMNP]2+ (A/A-NMe) and their racemic mixture [Ru(phen)2p-DMVP]2+(dl-NMe)were synthesized and the activity research were performed by electronic absorption titration, fluorescence spectrum, circular dichroism (CD), FRET experiments and NMR spectrum. The UV-Vis and fluorescence spectrum results indicate that two chiral enantiomers may bind to G-quadruplex through intercalative mode. CD spectrum reveals that the chiral enantiomers and the racemic complex can convert the structure of G-quadruplex. FRET experiment show that three complexes all can enhance the 7m value of G-quadruplex, and the binding affility of A-enantiomer is stronger than that of A-enantiomer.In chapter 4, a paire of chiral ruthenium complexes A/A-[Ru(phen)2p-HPIP]2+ (â–³/A-OH) and their racemic mixture [Ru(phen)2p-HPIP]2+(dl-OH)were synthesized and the activity research were performed by electronic absorption titration, fluorescence spectrum, circular dichroism (CD) and FRET experiments. The UV-Vis and fluorescence spectrum results indicate that two chiral enantiomers may bind to G-quadruplex through intercalative mode. CD spectrum reveals that the chiral enantiomers and the racemic complex can convert the structure of G-quadruplex. FRET experiment show that three complexes all can enhance the Tm value of G-quadruplex, and the binding affility of three complexes are little difference.