Our research focuses on the conformational properties of nucleic acids: conformation, conformational transitions, ligand binding, and the thermodynamics associated with conformation, conformational transitions and binding. We are primarily interested in how sequence context and environmental conditions influence these properties. We use a variety of biophysical techniques such as UV/Vis and circular dichroism spectroscopies, differential scanning calorimetry and isothermal titration calorimetry.
Although the Watson-Crick model of DNA as a right-handed double helical structure stands as the primary conformation in how we think about DNA, we now know that DNA is highly polymorphic: (A) DNA can exist as a single strand, duplex, triplex, quadruplex or even multiplex; (B) the duplex can either be right handed of left handed; and, (C), DNA can be sculpted into unusual higher order structures. Ultimately, the conformation and associated conformational properties of a segment of DNA is determined not only by its sequence context but also by the environmental conditions (i.e., temperature, pH, identity of counter ions and their concentrations, etc) under which it is prepared. Of particular interest recently are the structures formed from G-rich DNAs designated as quadruplexes. DNA sequences that have islands of G2-4 separated by 1 to 4 A or T bases can form a rich library of secondary structures with different molecularities, strand orientations, and guanine base conformation (i.e., syn or anti). Thus, we are investigating the structure, stability and ligand binding of DNA quadruplexes.
Industry Expertise (3)
Areas of Expertise (5)
University of Florida: Ph.D., Organic Chemistry
University of Florida: M.S., Chemistry
Michigan State University: B.S., Chemistry
ABSTRACT: Quadruplex structures arise from four coplanar G bases arranged in a Hoogsteen base pairing motif to create a central pore that can coordinate cations. The termini of eukaryotic chromosomes contain structures, known as telomeres, which are capable of forming ...
ABSTRACT: Genetic expansion diseases have been linked to the properties of triplet repeat DNA sequences during replication. The most common triplet repeats associated with such diseases are CAG, CCG, CGG, and CTG. It has been suggested that gene expansion ...
ABSTRACT: We have recently reported the cation-induced self-assembly of DNA oligomers of the general sequence C4T4G4T1-4G4 into high-molecular weight multistranded structures [Marotta, S. P., Tamburri, P. A., and Sheardy, R. D. (1996) Biochemistry 35, 10484−10492]. The architecture of the proposed structure consists of a series of four leafed G4 tetrads tethered together via one or two T1-4 strands and thus resembles a long four-sided hollow tube with periodic “pockets”. These pockets possess electrostatic, hydrogen bonding, and hydrophobic contact points and should be ideal candidates for the binding of small molecules...
ABSTRACT: The development of new molecules that bind strongly and selectively to nucleic acids expands the range of potential pharmaceutical agents whose mode of bioactivity is through interaction with DNA or RNA.'Metal complexes containing planar aromatic ligands have ...
ABSTRACT: Nucleic acid junctions are stable analogs of branched DNA structures which occur transiently in living systems. We show here that junctions which contain three double helical arms can be enzymatically oligomerized, using conventional sticky-ended ligation ...