LEAPS-MPS: Synthesis, Structural Analysis, and Characterization of Opioid Cyclic Tetrapeptides

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2). In this project, funded by the Mathematical and Physical Sciences Directorate and housed in the Chemistry Division, Professor Michael Ferracane and his students at University of Redlands will study the structure, properties, and opioid activities of a series of related cyclic peptides. This research will improve fundamental knowledge of cyclic peptide structure while assessing the scaffold’s therapeutic potential. Notably, the project will integrate new software/equipment into research and coursework at Redlands, and it will provide six undergraduate students from underrepresented groups with the opportunity to (1) engage in research projects on and off campus, (2) participate in a series of scaffolded professional development exercises, and (3) mentor similar students through on-campus programs. Professor Ferracane and his students will assess the structure-activity relationship of cyclic tetrapeptides to better understand their chemical structure, properties, and potential as opioid therapeutics. They will perform chemical synthesis, NMR analysis, and molecular modeling as well as a series of assays that measure solubility, membrane permeability, and opioid receptor binding. It is believed that distinct conformations impart a peptide with the ability to be soluble in water, passively permeate membranes, and bind the opioid receptors. The combined work will illuminate how a cyclic tetrapeptide’s unique sequence and environment affect its overall conformational landscape and then relate these findings to measured properties and opioid activities. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.