Vincent M. Rotello

Vincent M. Rotello

Professor of Chemistry, University of Massachusetts

Ph.D.: Yale University
Postdoctoral Training: National Science Foundation Postdoctoral Fellow, Massachusetts Institute of Technology

Research Interests

Architecture, conformational energetics, and reactivity are the three determinants of activity in enzymes. Isolation and observation of these features individually are difficult or impossible due to the complexity of the native macromolecular systems. Our research uses synthetic organic chemistry to create model systems that allow in-depth study of individual aspects of biomolecular behavior. We are currently targeting two major aspects of molecular function: electron transfer in flavoenzymes and conformational energetics of α-helices.

Flavoenzymes (redox enzymes that use flavin co-factors) are involved in key reactions in aerobic metabolism, biotransformations, and detoxification of xenobiotics. One of the key requirements for their activity is the correct geometry between the flavin and substrate. In order to recreate this geometry in a model system, we have designed a modular flavin receptor. This molecule uses hydrogen bonding to provide a defined host-guest geometry. We are currently using these receptors to provide insight into the mechanisms of flavoenzyme activity.

The rigidity of current synthetic receptors limits their ability to mimic biological hosts such as enzymes and antibodies. In order to overcome this difficulty, we are creating a series of peptide-based molecular clefts. In these systems, the ability of peptide α-helices to undergo conformational adjustments will be used to create binding sites sufficiently flexible to allow effective modeling of biophysical properties. The clefts use both natural and unnatural amino acid sidechains to provide recognition elements for biologically interesting target molecules