NanoFun/MoLife Colloquium

“Targeting the Terminus to Achieve Site-Selective Recognition of Peptides and Proteins”

Cucurbit[n]uril synthetic hosts bind selectively to aromatic amino acid residues at the N-terminus of peptides and proteins. Recognition is mediated by simultaneous inclusion of the hydrophobic sidechain within the cavity of the cucurbit[n]uril, and electrostatic attraction of the N-terminal ammonium and peptide NH groups with the carbonyl oxygens on the portals of the cucurbit[n]uril. These interactions enable the selective binding of an N-terminal aromatic residue, such as phenylalanine (Phe) or tryptophan (Trp), versus non-terminal aromatic residues, non-aromatic residues, and amino acids by factors ranging from 10-10,000-fold in binding affinity. Affinities in aqueous solution are excellent compared to other synthetic receptors, but the limit of dissociation constants is on the order of 0.1-1 micromolar, which is too high to be practical for the development of medical diagnostics or useful biochemical separation techniques. This presentation will cover our recent work that addresses challenges in these areas, including recognizing natural proteins, monitoring protease activity and inhibition, achieving nanomolar affinity, and exploring novel means for separations.