Dr. McCurdy's Research
Overall Theme. Bioorganic Chemistry -- Noncovalent Interactions: The following descriptions are of separate but conceptually related ongoing research projects in the McCurdy lab. It is the ultimate goal of each project to understand noncovalent interactions of interesting biochemical processes.
Project area 1:
Synthesis of organic molecules designed to mimic calcium signaling in cells by noncovalently binding and releasing calcium ions in response to light.
Background. Calcium is a ubiquitous second messenger, helping translate external hormone signals into internal cellular events. It has been discovered that in certain cell types, calcium is released in an oscillatory fashion inside the cell. Interestingly, the frequency of the oscillation is proportional to the concentration of extracellular agonist. It is the goal of this research to synthesize photo-reversible calcium-specific chelators which may be tuned with light to mimic these oscillations. In this manner, the role of calcium oscillations in cells may be probed.
The water-soluble organic molecules to be synthesized in the McCurdy laboratory are made of a photochromic scaffold - which provides light-sensitivity - combined with chelating carboxylate ligands -which provide calcium ion selectivity. This research involves multistep organic synthesis and NMR binding titration studies.
Project area 2.
Investigation of the energetics of amino acid side-chain interactions in simple artificial proteins.
Background. Aromatic groups are not only hydrophobic, but also electron-rich. As such, the face of an aromatic ring can act as a hydrogen-bond acceptor and can stabilize positively-charged species. In proteins, the aromatic residues are phenylalanine, tyrosine, and tryptophane. The "binding" of cationic cofactors, substrates, transition states, and side chains in the folded proteins has yet to be fully explored.
Protein models such as synthetic peptide alpha helices can be used to determine the energy of stabilization of a noncovalent interaction between two side chains a distance of (i, i+4) apart along the protein helix. Circular dichroism spectroscopy is used in this research to compare the stability of model alpha helix variants that incorporate natural and unnatural amino acids in positions (i, i+4) and (i, i+5).