Gerig Group Research

Small Molecule-Peptide Interactions

Usual laboratory studies of peptides and proteins may give an incomplete picture of the structures of these molecules and how they achieve their biological effects. Such studies typically examine materials that are highly homogeneous, dissolved in well-defined solutions that may contain a simple buffer system and perhaps some salt. The cellular environment where the subject molecule actually operates may be much more complex, containing high concentrations of many large and small molecules.
Developments in our group over the past few years have provided NMR tools for study of the interactions of small molecules with peptide or proteins. Our experiments address the following types of questions regarding the influence of small molecules on the structures of peptides and proteins. What is the nature of a small molecule-peptide interaction? Are these interactions specific for particular atoms? Are the interactions stronger or weaker than what would be expected for simple collisions of the small molecule with the peptide? What is the nature of the competition between water molecules and small molecules for interacting with a protein or peptide surface? Do particular interactions favor a given conformation or, conversely, does a certain conformation favor a particular type of small molecule interaction?

Fluorous Reaction Systems

Liquid perfluorocarbons generally are immiscible with hydrocarbons, although some fluorocarbon-hydrocarbon systems mix at elevated temperatures conveniently achieved in the laboratory. The ability of such non-aqueous systems to exist as two phases at low temperature but as a single phase at higher temperature has led to development of strategies for doing chemical synthesis that rely on the temperature-dependent phase behavior to achieve separation of reactants from products and reaction catalysts. These so-called “fluorous” or “biphasic” methodologies have received much attention.
It was a goal of our work to provide experimental information about the interactions between a dissolved molecule and all components of a fluorous reaction system. The major experimental tool is detection of solvent spin-solute spin dipolar interactions as reflected in intermolecular nuclear Overhauser effects.
Ionic Liquid Systems
Ionic liquids are materials composed solely of ions that are liquid at temperatures near room temperature. They are attractive alternatives to the usual solvents used for chemical reactions because they have no vapor pressure and, thus, cannot escape into the environment. Ionic liquids have been found to be useful solvents for cellulose, an otherwise generally refractory solute. We have launched an effort to study interactions between dissolved sugars and the components of ionic liquids to determine the reasons for the enhanced solubility of cellulose and other polysaccharides in these systems. Initial study is focused on overcoming experimental issues that will have to be dealt with in performing reliable intermolecular NOE experiments.