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

该项目支持温莎大学Trant实验室开发的一项新兴技术，以帮助研究人员和制药公司制造一类药物和研究工具，比目前的方法容易得多。多肽、氨基酸短链和概念上的短蛋白质通常是研究人员更好地了解生物学和治疗疾病的优秀候选药物或探针。就像所有的分子一样，形式就是功能，多肽通过编码到氨基酸序列中的固有扭曲来采用特定的构象，也通过半胱氨酸残基在多肽的不同部分之间进行交联。半胱氨酸上有一个硫，这使得它可以与另一个半胱氨酸氨基酸上的另一个硫原子结合，从而形成药物的形状。当只有一个二硫键存在时，这相对简单，但随着更多二硫键的引入，这变得越来越复杂，这意味着任何研究团队都需要专业的多肽有机化学家来设计和排除故障。此外，选择性地形成键意味着需要许多不同的化学步骤，往往在每一步之间进行纯化，大大增加了成本。我们有一个简单的通用解决方案，它使用热量作为唯一的触发器来制造这些材料。该项目的这一组成部分将支持我们将我们的方法应用于越来越多的多肽实例的实践，以确保工业合作伙伴的兴趣，无论是那些直接将其用于特定项目(Cotinga)的公司，还是希望将该技术作为“工具包”营销的精细化工公司(Sigma-Aldrich)。这些产品将继续在加拿大制造，并在全球范围内销售，以造福于安大略省温莎以及加拿大的经济和生物技术行业。

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.