Peptides are attractive targets for drug discovery. As compared to traditional small molecules, peptides showcase enhanced selectivity and binding affinity. Despite their therapeutic potential, the limited solubility and short half-life of peptides has hampered their uptake into the clinic. One avenue for improving the competence of peptides as drugs is the introduction of unnatural amino acids, those outside of the 20 canonical amino acids, into peptides. Research in the Bloom lab is working towards a high-throughput strategy for inserting unnatural amino acids into peptides using dehydroalanine (Dha) residues as latent pro-amino acids. In this way, libraries of peptide variants can be rapidly assembled and used for screening against a multitude of diseases. In addition, the Bloom lab is using Dha residues to tackle other problems in peptide medicinal chemistry, including macrocyclization, helix-induction, and conjugation to carrier proteins. The Bloom is also pioneering the use of biocompatible photocatalysts to directly modify endogenous peptides with functional groups (phosphates, PEG, fatty acids) that improve their potential use as drugs.
