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

I2I 阶段 1a：开发热敏保护半胱氨酸残基以控制二硫键形成

• 批准号: 561575-2021
• 负责人: Trant, John
• 金额: $ 9.11万
• 依托单位: University of Windsor
• 依托单位国家: 加拿大
• 项目类别: Idea to Innovation
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=724271
• 关键词: I2I; Phase; 1a; Development; thermally

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.

该项目支持由温莎大学Trant实验室开发的一项新兴技术，该技术帮助研究人员和制药公司制造一种子类药物和研究工具，比目前的方法容易得多。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。与所有分子一样，形式即功能，肽通过编程到氨基酸序列中的固有扭曲以及通过半胱氨酸残基在肽的不同部分之间的交联来采用特定的构象。半胱氨酸上有一个硫，这使得它能够与另一个半胱氨酸氨基酸上的另一个硫原子键合，从而为所产生的药物提供形状。当只有一个二硫键存在时，这是相对简单的，但随着更多的引入而变得越来越复杂，这意味着任何研究团队都需要有专业的肽有机化学家来设计和解决方法。此外，选择性地形成键意味着需要许多不同的化学步骤，通常每个步骤之间的纯化大大增加了成本。我们有一个简单的通用解决方案，使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的简化实践，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，无论是直接将其用于特定项目（Cotinga）的公司，还是希望将该技术作为“试剂盒”销售的精细化学品公司（Sigma-Aldrich）。“这些将继续在加拿大制造，并销往世界各地，以造福温莎，安大略，加拿大经济和生物技术产业。