In 1957, A. Rich, D. Davies, and G. Felsenfeld produced a triple-stranded form of nucleic acids while studying synthetic nucleic acids. Nucleic acid triple helices currently are the focus of considerable attention. The attention in large part is due to the potential biomedical applications of triplex structures, which include the specific control of cellular processes, such as transcription and replication, and the mapping of megabase DNA through the selective cleavage of specific DNA duplex domains etc. There is a Third Strand Binding Code and a high level of specificity of recognition of AU/T and GC base pairs in nucleic acid triplets. Our current research mainly focus on the area of nucleic acid therapeutics. We are studying the fundamental interactions between DNA and various ligands, including DNA as a ligand, by looking at the effect of sequence variations, base modifications, presence of cations, drugs etc., on the stability of various structural forms of DNA. During the past year, there has been a lot of evidence to demonstrate that cations (such as Mg2+, Zn2+) and DNA intercalating ligands (such as ethidium, daunomycin) can induce and stabilize formation of nucleic acid triple helices (such as 2d[G(AG)5]d[C(TC)5] and d[G(TG)5]d[G(AG)5]d[C(TC)5]). We will further study the molecular mechanism of interaction of various drug molecules and cations with various sequences of DNA triplexes using the facilities of the Computer Graphics Lab.
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