Advances in Amino Acid Chemistry and Peptide Mimicry

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Natural Science research on the molecular recognition of peptide structures is a fundamental pursuit with remarkable potential to impact on various fields. For example, the use of peptide-based drugs in medicine is predicted to grow to a global market value of US $48.04 billion by 2025. Similar growth in interest in peptides is paralleled by other fields due in part to utility in information storage, catalysis and materials science. Flexible and degradable, peptides serve transient roles in food and endogenous messengers in physiological systems; however, such properties are often drawbacks for tasks requiring rigidity and longer duration of action. Penetrating the heart of this predicament, our research program in peptide mimicry targets tools for systematically studying structure-activity relationships to obtain insight about active conformers and means to improve their pharmacokinetic properties.***Focused on novel organic-synthesis methods to prepare densely functionalized molecules for examining influences of electronic and structural forces on peptide geometry and recognition, our NSERC-Discovery Grant program has introduced effective solution- and solid-phase chemistry for making three major classes of peptide mimic: amino acid isosteres, heterocycle-peptide hybrids, and peptide macrocycles. Building on a solid foundation of preliminary results and integrated in collaborative applied research, our fundamental program is now ideally positioned to accelerate advances on pressing contemporary issues in peptide science. Specifically, the importance of ionizable side chains, turn conformers and helical backbone geometry will be examined to enhance peptide cell permeability and bioavailability, to combat drug-resistance and to disrupt self-aggregation. ***Chemical synthesis of the proposed peptide mimic targets embodies a formidable challenge for training highly qualified personnel, who are charged to develop functional-group tolerant methods for selective peptide modification to introduce isosteric residues, to install conformational constraint, and to cyclize the sequence. Studying the chemistry of peptide mimicry in strategic collaborations, students receive pertinent training to become leaders knowledgeable in modern synthetic chemistry, in spectroscopic techniques to explore the impact of molecular constraint on peptide geometry, and in communication with our collaborators to understand structure-activity relationships. ***Study of the proposed peptide mimic targets is paramount for tackling critical unmet medical needs for developing new therapy to treat microbial infection and amyloid diseases for improved quality of life in Canada. Focused primarily on organic synthesis in peptide-based medicinal chemistry, our program benefits from broad scientific interests and aptitude for collaborative natural science research to seize upon discoveries with impact on various fields, including polymer science, catalysis and natural product synthesis. **