Synthesizing Small Molecule Inhibitors of HDL Uptake via the SR-BI Receptor Protein

Mentors: Chris Dockendorff, Willmen Youngsaye, Partha Nag

The goal of Conor’s project was to synthesize small molecule inhibitors that inhibit lipid transport by the receptor protein Scavenger Receptor, Class B, Type I (SR-BI). By synthesizing potent inhibitors of SR-BI, one can potentially control a number of biological processes including: female fertility, inhibition of viral entry into cells, and lipid metabolism. Conor and his mentors sought to synthesize a molecule that affected SR-BI activity, so that it could be used in future studies, to elucidate the role of SR-BI in these processes.

Two chemical compounds had been previously discovered to be potent inhibitors of SR-BI, and were therefore prioritized for further analysis. Using these two compounds (Indoline and the Ugi Peptide) as backbones, Conor synthesized many analogs, and discovered two new compounds with high potency and potentially improved properties. The Ugi Peptide was used to synthesize compounds that were far more soluble, so these will potentially take a leading role in future exploration of SR-BI function, and inhibitors.



Conor, a senior at Cambridge Rindge and Latin School, synthesized chemical compounds that inhibit a specific receptor protein with roles in lipid metabolism, fertility, and entry of viruses into human cells.