Broadly, research in the Guarracino Group is in the field of chemical biology. Overall, we synthesize compounds that mimic the structure of small biological proteins and then test their ability to either abrogate, imitate or improve protein function. Specifically, we design and develop macrocyclic peptides that mimic the sequence and structure of hormones vasopressin and oxytocin. The changes incorporated into our compounds, as compared to the natural hormones, are systematically chosen to improve upon the stability of the original hormones. Subsequently, we test the cyclic peptides for their functionality. We subject each peptide, the “parent” hormones, and a linear peptide control, to a panel of peptide-degrading proteases and trace the percent degradation over different intervals of incubation at human body temperature. Additionally, in a competition Enzyme-Linked Immunosorbent Assay (ELISA), we test the ability of the compounds to displace vasopressin or oxytocin from binding their membrane receptors. Future studies will include testing the capabilities of our compounds to illicit the same cellular response of the “parent” hormones or block the hormone function entirely. Both vasopressin and oxytocin are involved in a number of biological processes, from maintenance of electrolyte balance to cell signaling in the reproductive organs. Subsequently, their mis-regulation is often implicated in disease and thus a call for new hormone therapeutics is the subject of ongoing research. The development of our compounds and the assays we perform supports their candidacy as first generation pharmaceuticals.
