Proposal for a Market Assessment for thermally protected cysteines to rapidly obtain complex peptides with multiple disulfides

将进行一项市场研究，以评估一种新的化学技术商业化的可行性，该技术将允许在给定的肽或氨基酸链内简单而廉价地形成多个半胱氨酸二硫键。该技术最近在8月6日向USPTO提交了临时专利申请62/883332。当两个半胱氨酸氨基酸使用它们的硫原子形成一个新的化学键时，就形成了二硫桥。这些桥帮助将一维肽链组织成确定的三维形状。当一个肽含有多个不同的半胱氨酸氨基酸时，可能会有多种不同的三维形状，但通常只形成一种，因为这些键的形成是由生物体中发现的其他伴侣蛋白介导的。二硫键在许多小肽中非常重要，包括胰岛素和芋螺毒素（它们是用于控制严重疼痛的阿片类药物的潜在镇痛剂和非成瘾性替代品）。这些分子不容易用传统的生物技术制造，因为标准的细菌表达系统缺乏适当的细胞机制来确保正确的二硫键形成。因此，许多这些复杂的分子是使用固相肽合成化学地制造的，其中需要复杂的多步骤方案来确保形成正确的二硫键：在一些芋螺毒素中，有10个半胱氨酸，这使得二硫键的许多可能组合，其中只有一个是活性的。这些多步骤的程序昂贵且收益低。Trant和共同发明人设计了一种新的可刺激的方法来选择性地产生这些二硫键，这将显着降低获得这些材料所需的复杂性，成本和时间，使其中许多材料首次在商业上可行。这项技术将是高度破坏性的。我们希望评估将确认这项技术具有商业利益，并将确定影响采用的因素，关键利益相关者和商业化合作伙伴，以及改善加拿大和世界各地数百万人生活的新方法的必要性。

A market study will be conducted to assess the viability of commercializing a new chemical technology thatwill allow for the simple and inexpensive formation of multiple cysteine disulfide bridges within a givenpeptide-or chain of amino acids. This technology has recently had a provisional patent application 62/883332filed on August 06 to the USPTO. Disulfide bridges are formed when two cysteine amino acids use their sulfuratoms to make a new chemical bond. These bridges help organize the one-dimensional peptide chains intodefined three-dimensional shapes. When a peptide contains multiple different cysteine amino acids, multipledifferent three-dimensional shapes are possible, but generally only one is formed as the formation of thesebonds is mediated by other chaperone proteins found in the organism. Disulfide bridges are extremelyimportant in a number of small peptides including insulin and the conotoxins (which are potential analgesicsand non-addictive replacements for opioids for severe pain control). These molecules cannot be easily madeusing traditional biotechnology as standard bacterial expression systems lack the proper cellular machinery toensure that the correct disulfide bonds are formed. Consequently, many of these complex molecules are madechemically using solid-phase peptide synthesis where complex multi-step protocols are required to ensure thatthe correct disulfide bonds are formed: in some conotoxins there are 10 cysteines which makes for manypossible combinations of disulfide bridges, only one of which is active. These multistep procedures areexpensive and low-yielding. Trant and co-inventors have designed a new stimuli-triggerable method forgenerating these disulfide bridges selectively which will significantly decrease the complexity, cost, and timerequired to access these materials making many of them commercially viable for the first time. This technologywill be highly disruptive. We expect that the assessment will confirm that there is a commercial interest in thistechnology and will identify factors affecting adoption, key stakeholders and commercialization partners, andthe need for new approaches to improve the lives of millions of people in Canada and around the world.