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

该项目支持温莎大学特兰特实验室开发的一项新兴技术，帮助研究人员和制药公司比现有方法更容易地制造药物和研究工具的子类。肽，短链氨基酸和概念上短的蛋白质，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，多肽既通过编程到氨基酸序列中的固有扭曲，也通过半胱氨酸残基在多肽的不同部分之间的交联来形成特定的构象。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。当只有一种二硫键存在时，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肽有机化学家来设计和排除这种方法。此外，选择性地形成键意味着需要许多不同的化学步骤，通常在每个步骤之间进行纯化，这大大增加了成本。我们有一个简单的通用解决方案，用热作为制造这些材料的唯一触发器。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肽实例，以确保工业合作伙伴的利益，包括那些直接将其用于特定项目的公司（Cotinga）和精细化工公司（Sigma-Aldrich），这些公司希望将该技术作为“套件”进行市场推广。这些产品将继续在加拿大生产，并销往世界各地，以造福温莎、安大略省和加拿大的经济和生物技术产业。

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.