Synthesis and evaluation of rationally designed small molecular libraries for G-quadruplex selective DNA photocleavage

textDNA can fold into highly stable structural conformations known as G-quadruplexes (G4). Research has suggested that G4 DNA may play a role in the regulation of gene expression and it has been linked with several diseases including Werner's Syndrome, Bloom's Syndrome, and cancer. In order to better understand the biological roles of G4 DNA, small molecules that can be used to selectively detect these structures in a time-dependent manner were designed. These G4 DNA probe candidates bind to and photocleave G4 DNA, allowing analysis of the cleavage products as well as temporal detection of G4 DNA. The synthesis, characterization, and structure activity relationships (SAR) of two rationally designed libraries are discussed. The photocleavage activity and binding selectivity for these compounds is evaluated in both the context of single stranded DNA and plasmids. The development of a program that can be used to search genome sequences for G-triplex (G3) DNA, a potential folding intermediate to G4 DNA that may have its own biological roles, is also discussed.Biochemistr