Development of Novel Synthetic Methodologies: Any chemical research program that studies the dynamics of biological systems requires entry to the desired substrates. This is the primary goal of my research plans, to develop synthetic methodologies to expedite the asymmetric preparation of target molecules, especially organophosphorus and heterocyclic systems. Since evaluation of biological response often requires synthesis of many analogues of a target structure, development of novel strategies for their construction is critical. Currently, our research in this area focuses on the synthesis of nitrogen heterocycles, organophosphorus chemistry, and the asymmetric synthesis of novel amino acids and acetylcholine derivatives.

Synthesis of Cocaine Antagonists: Cocaine abuse continues to be a serious societal and medical concern in the United States. Currently, there is no one pharmacological treatment to block the desire or reduce the craving to use cocaine. Additionally, there are a number of basic questions concerning the reinforcing properties of cocaine at the molecular level which still needs to be answered to fully understand the causes of abuse. The research program underway centers on the synthesis and biological evaluation of novel cyclopropane analogues of cocaine as potential antagonists at the dopamine transporter. The new cocaine analogues should provide new insight to the binding of cocaine at the dopamine transporter and potential new lead structures for anticraving drugs.

Neuropeptides and Brain Function: Almost all peptides made by neurons will affect specific target cells of the central and peripheral nervous system. Unfortunately, the specific signaling advantages of peptides are not yet obvious. Furthermore, with very few exceptions, no peptides have yet been linked selectively to a given functional system in the brain or correlated in any exclusive manner with any pathological state. Consequently, the role of neuropeptides in nerve transmission, learning and memory, mental health, and the general function of the brain require further investigation. In our laboratory we are currently examining the interaction of neuropeptide Y (NPY), a 36 amino acid peptide, with a variety of systems in the central nervous system. Our present work focuses on the interaction of fragments, derived from enzymatic degradation of the parent molecule, with opioid receptors in the brain. We believe that this work will provide a better understanding of the nociceptive function of NPY.