The long term objective of this project is to elucidate the possible roles played by DNA conformations on the gene regulatory processes. Our short term goals are the physico-chemical studies of DNA oligonucleotides which have the potential to form unusual conformations. The current proposal will focus only on the formation of intramolecular structures from systems having the common hairpin motifs. Particular attention will be paid to the studies of triple helix and pseudoknot formation from a single strand.
The specific aims for the next few years will be: (1) To synthesize and purify oligonucleotides which are capable of forming unusual intramolecular DNA conformations such as hairpins, triplexes, and pseudoknots. (2) To characterize these unusual conformations and to delineate conditions which favor these structures by electrophoretic and spectroscopic means. (3) To investigate the kinetics of transformation and possibly mechanisms of some conformational transitions. (4) To obtain thermodynamic properties of conformational transitions by means of differential scanning calorimetric measurements and spectroscopic melting experiments. (5) To study the binding characteristics of some intercalative as well as non-intercalative ligands to these unusual conformations.
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