University of Nebraska-Lincoln
Identifying Peptide-Receptor Interactions using Aryl Diazonium-Labeled Peptide Ligands
Dr. Elizabeth Schram YI Oral Competition
Monday, June 26, 2023, at 04:15 pm - 04:30 pm
Endogenous bioactive peptides, for example, neuropeptides and peptide hormones, are a class of signaling molecules that play pivotal roles in maintaining cardiovascular, reproductive, gastrointestinal, and metabolic health. Dysregulation of peptide signaling is associated with diseases such as cancer, multiple sclerosis, Alzheimer's, diabetic nephropathy, and many more. However, despite the growing interest, the receptor proteins for many disease-relevant bioactive peptides are currently unknown, severely limiting their potential as therapeutic targets.
In a quest to discover novel peptide-protein interactions, and unveil molecular mechanisms underlying diseases, we report a proximity induced labeling strategy using aryl diazonium-modified bioactive peptides to covalently label corresponding membrane-bound receptors.
We describe the design principles needed for the synthesis of aryl-diazonium modified bioactive peptides to achieve efficient receptor labeling and demonstrate that a peptide's affinity to a given receptor can be harnessed to specifically label interacting proteins on living cells under physiological conditions. We hypothesize that the developed protein labeling strategy can be used for the enrichment and isolation of membrane proteins in an unbiased fashion. Long-term, this research may aid in identifying new therapeutic targets for a number of diseases caused by dysregulated cell-cell signaling peptides.
Sheryl Sharma obtained her B.Sc and M.Sc in chemistry from University of Delhi and Thapar Institute of Engineering and Technology, India. She worked as an executive organic chemist at the R&D facility of Panacea Biotec before switching to working as a patent attorney at Lakshmikumaran and Sridharan, New Delhi, India. She is currently a graduate student in Dr. James Checco’s lab at the University of Nebraska-Lincoln where her research focuses on developing bioactive peptides as labeling probes for the discovery of novel protein-protein interactions.