Small molecule recognition of homopurinenucleic acid structures

Physical characterization;Nucleic acids;Small molecule binding;Assembly;Intercalation

Persil Cetinkol, Ozgul ; Chemistry and Biochemistry

University:Georgia Institute of Technology

Department:Chemistry and Biochemistry

关键词: Physical characterization;    Nucleic acids;    Small molecule binding;    Assembly;    Intercalation;   

Others  :  https://smartech.gatech.edu/bitstream/1853/29739/1/persilcetinkol_ozgul_200808_phd.pdf

美国|英语

来源: SMARTech Repository

【 摘 要 】

The thesis topic entitled above involves the use of small molecules as a general means to drive nucleic acid assembly and structural transitions. We have shown that coralyne, a crescent-shaped small molecule, can assemble homo-adenine DNA and RNA sequences into anti-parallel duplexes at neutral pH, a structure containing putative purine-purine (A*A) base pairs that is otherwise unstable.The importance of the structure of the small molecule in the recognition and stabilization of A*A base pairing has been established by experimental evidence.We further provide structural evidence for the putative A*A base pairing that is stabilized by coralyne and molecules of similar size and shape.Our hypothesis that planar molecules that are slightly too large to intercalate Watson-Crick base pairs might intercalate the larger purine-purine base pairs has led to the design of a new class of small molecules that tightly bind purine-purine duplexes with excellent selectively.We have demonstrated that azacyanines can exhibit strong and selective association with a human telomeric sequence that forms a unimolecular G-quadruplex in solution.The synthetic accessibility of azacyanines makes this class of molecules amenable to library preparation for high-throughput screening.Together, the findings reported in this thesis provide further evidence for the robust and versatile nature of selective small molecule recognition of nucleic acids, especially purine-purine duplexes.