UC San Diego

Gold nanoparticles (AuNPs) have gained popularity in the development of in vitro diagnostics for their distinct physical and optical properties. More specifically, the surface plasmon resonance (LSPR) can be exploited via aggregation to generate a significant absorption band shift in the visible region of the electromagnetic spectrum, resulting in a pronounced red-to-blue color change that is visible to the naked eye. Our group has developed an intuitive and accessible, label-free diagnostic platform that takes advantage of the key proteolysis step in viral replication by designing cleavable peptide intermediates to interface with gold nano colloids. Peptides are an effective probe due to their diverse and tunable functional groups found on amino acid side chains, which can interact with AuNPs through electrostatic, dithiol bridging, or amphiphilic interactions to promote aggregation. First, we determine the effects of modifying AuNPs with various surface ligands on aggregation propensity in the presence of charged, thiolate, or aromatic amino acids. The characterization study will then inform a final peptide design that encompasses all three molecular interactions which will be used to colorimetrically detect the coronavirus main protease. Second, we build on a well-established zwitterionic peptide design for electrostatically interfacing negatively charged AuNPs by providing additional optimizations of peptide design through the addition of lysine to arginine groups. An optimized peptide probe is then used to colorimetrically detect the norovirus main protease, additionally demonstrating the generalizability of this diagnostic platform.