I2I Phase 1a: Development of thermally-sensitive protected cysteine residues for controlled disulfide bond formation

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This project supports an emerging technology developed by the Trant Lab at the University of Windsor to help researchers and pharmaceutical companies make a subclass of drugs and research tools far more easily than current methods. Peptides, short chains of amino acids, and conceptually short proteins, are often excellent drug candidates or probes for researchers to better understand biology and to treat disease. Like for all molecules, form is function, and peptides adopt specific conformations both through the inherent twists programmed into the amino acid sequence, but also through cross-links between different parts of the peptides through cysteine residues. Cysteine has a sulfur on it, and this allows it to make a bond to another sulfur atom on another cysteine amino acid, providing shape to the resulting drug. This is relatively simple when only one of these disulfide bonds is present, but becomes increasingly complex as more are introduced, meaning that any research team needs to have specialist peptide organic chemists to design and troubleshoot the approach. Furthermore, forming the bonds selectively means that the many different chemical steps are needed, often with purification in between each step greatly increasing costs. We have a simple general solution that uses heat as the only trigger to make these materials. This component of the project will support our reduction-to-practice where we apply our approach to more and more peptide examples to secure the interest of industrial partners, both for those that are using it directly for a specific project (Cotinga), and for fine chemical companies (Sigma-Aldrich) that would look to market the technology as a "kit." These will continue to be made here in Canada and sold worldwide to benefit the Windsor, Ontario, and Canadian economy and biotech industry.