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，以评估将一种新的化学技术商业化的可行性，该新技术将允许在给定的多肽或氨基酸链内简单且廉价地形成多个半胱氨酸二硫键。这项技术最近于8月6日向美国专利商标局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新的化学键时，就形成了二硫键。这些桥接有助于将一维肽链组织成定义的三维形状。当一个肽包含多个不同的半胱氨酸氨基酸时，可以形成多个不同的三维形状，但通常只形成一个，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是极其重要的，包括胰岛素和芋螺毒素(它们是阿片类药物的潜在镇痛剂和非成瘾性替代品，用于剧烈疼痛控制)。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，这些复杂分子中的许多都是使用固相多肽合成的，其中需要复杂的多步骤方案来确保正确的二硫键的形成：在一些芋螺毒素中有10个半胱氨酸，这使得许多可能的二硫键组合，其中只有一个是活性的。这些多步骤的过程既昂贵又低收益。Trant和共同发明者设计了一种新的刺激触发的方法来选择性地产生这些二硫键，这将显著降低获得这些材料的复杂性、成本和时间要求，使其中许多材料首次在商业上可行。这项技术将具有极强的颠覆性。我们预计，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、主要利益攸关方和商业化合作伙伴，以及需要新的办法来改善加拿大和世界各地数百万人的生活。

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.