Amy Deveau’s laboratory publishes paper in 'Bioorganic and Medicinal Chemistry Letters'
The laboratory of Amy Deveau, Ph.D., associate professor of chemistry, recently published a paper in the journal Bioorganic and Medicinal Chemistry Letters (2012, 22, 6801-6805).
Students David Martin (COM, 12’) and Paul FitzMorris (CAS, Biochem/MedBio, 10’) developed a new synthetic approach to synthesize Ring C bridged derivatives of naltrexol. This new synthetic method, in conjunction with data from ongoing research, is being applied to understand conformational preferences in naltrexol and how the accessible conformations of Ring C relate to trends in in vitro functional binding for the G-protein coupled mu and kappa opioid receptors.
In the course of the research, the team discovered a novel derivative that functions as a dual kappa opioid agonist / mu opioid receptor antagonist. The team confirmed the compound’s structure by NMR Spectroscopy, mass spec, and X-Ray Crystallography.
The X-Ray structure was solved in collaboration with Bo Li, Ph.D., director of X-Ray Crystallography Center at Boston College. In vitro assays were completed in the lab of Richard Rothman, M.D., Ph.D., from the National Institutes of Health by coauthors Mario Ayestas, Ellicott J. Sally, and Christina M. Dersch. Overall, the potent compound has interesting chemical and biological properties and could be used therapeutically or as a biochemical probe.
Deveau’s paper was an invited contribution for a special journal issue in BMCL that was dedicated to the numerous contributions of Timothy L. Macdonald, Ph.D., in the field of medicinal chemistry. Macdonald, of the University of Virginia, was Deveau’s Ph.D. advisor. Contributions for the special journal issue were selected in part from invited presentations given at a Research Symposium held in April 2012 in Macdonald’s honor.