We develop and use synthetic chemistry to access robust peptide and protein mimics for drug design and chemical biology tools. Topics include: the effect of unnatural amino acids on folding and function, including molecular recognition and catalysis; medicinal chemistry; peptide chemistry; chemical biology.

Peptides modulate a variety of biological responses, including as hormones and neurotransmitters. Occupying the space between small molecules and biologics, they have also been pursued to target protein-protein interaction surfaces. However, strategies are needed to convert them into more stable molecules while retaining
the bioactivity of the native peptides, ideally employing scaffolds that can adopt precise secondary structures while being amenable to rapid derivatization for library synthesis and screening.

Towards that goal, we develop new methods for late-stage peptide functionalizations, and devise new strategies for the synthesis and conformational control of highly substituted peptidomimetics. This includes 1 the synthesis and study of N-aryl peptides as tunable precursors for kethydrazone and ketoxime ligations, 2 the development of new methods for chemoselective functionalizations of azapeptides, and 3 the design and application of new conformationally-constrained N-substituted glycine, peptoid monomers. This presentation will provide an overview of the new broadly applicable tools for peptide mimicry developed in the Proulx lab, with emphasis on synthetic method development.