Our laboratory is interested in topics at the interface of Chemistry and Biology, spanning the spectrum from synthetic organic chemistry to exploring the folding, bio-orthogonal reactivity, and catalytic activity of peptide mimics.
Progress in peptide mimicry requires the use and discovery of artificial building blocks that (1) are able to maintain or expand the side-chain diversity of natural amino acids, (2) impart greater protease resistance, (3) adopt precise secondary structures, and (4) are easy to synthesize. We are particularly interested in unnatural amino acids that closely resemble the backbone of natural amino acids, such as aza-amino acids and N-substituted glycines (peptoids). For more information on these classes of peptidomimetics, please see below.
Azapeptide (left) and peptoid (right) structures vs peptides (center):
Aza-amino acids are unnatural amino acids where the alpha carbon has been replaced by a nitrogen atom. The C to N exchange in azapeptides leads to: (a) loss of chirality, (b) greater chemical stability, (c) improved resistance to proteases, and (d) an increase in rigidity, inducing turns in certain azapeptide sequences due to the lone pair - lone pair repulsion of the two adjacent nitrogen atoms. The ability to improve the stability of peptides, while rigidifying secondary structures and keeping the position of the side-chains intact, make azapeptides a unique class of peptidomimetics. In addition to these advantages, libraries of azapeptides can be efficiently synthesized using simple submonomer procedures, where the aza-amino acids are built step-wise directly on solid-phase using commercially available reagents.
Submonomer azapeptide synthesis procedure (left) and examples of validated side-chains added via this approach (right):
Please contact Prof. Caroline Proulx for more information.