Novel biomaterial for enantiomer separation

项目总结 手性药物的分离、分析和拆分方法的发展 对医药发展的重要兴趣。同一化合物的两个对映体可以 具有相同的物理或化学性质，但在相互作用方式上显示出显著的差异 在人体系统中(即，关于它们的药理学、毒理学、药动学和 新陈代谢)。因此，药物的手性分离对于消除有害物质具有重要意义。 从制剂中得到的对映体。对映体的分离通常是通过高选择性的. 在手性固定相中使用手性选择剂的高效液相色谱 阶段(CSP)。CSPs可以由几种类型的分子组成，包括多糖。 (如直链淀粉和纤维素)和蛋白质(如白蛋白、酶)等。只有几个人 尽管蛋白质具有独特的对映体选择性，但仍被研究用作高效液相CSP。 属性。遗憾的是，目前基于蛋白质的CSP负载能力低，价格昂贵 做好准备，而且稳定性有限。显然，市场对酶和蛋白质的需求-- 一种承载能力高、降解少、货架扩展的CSP分离方法 生活。基于我们通过NSF的i-Corps计划进行的市场调查采访 在我们的平台生物材料技术上，明确了手性柱的技术 没有改变，这一领域的创新是令人向往的。邦德韦尔科技的目标是 在我们创新的基础上，开发一种用于CSP的新型大容量蛋白质选择器 生物材料。我们的生物材料的独特品质解决了目前手性的所有局限性 CBHS。在这项拟议的第一阶段可行性工作中，我们将首先表达手性选择器 酶纤维二糖水解酶(CBH I)，并形成我们的生物材料，我们将在 生物材料的功能，确保正确的折叠。然后我们将准备我们的材料作为 一个CSP。最后，我们将测试我们的生物材料分离贝塔对映体的能力。 阻断药物、心得安和阿普洛尔。

PROJECT SUMMARY The development of methods for the separation, analysis and resolution of chiral drugs is of important interest for pharmaceutical development. Two enantiomers of the same compound may have the same physical or chemical properties, but show marked differences in how they interact in a human system (i.e., regarding their pharmacology, toxicology, pharmacokinetics and metabolism). Thus, the chiral separation of drugs is important to eliminate the unwanted enantiomer from the preparation. Separation of enantiomers is typically achieved by high- performance liquid chromatography (HPLC) where a chiral selector is used in a chiral stationary phase (CSP). CSPs can be composed of several types of molecules, including polysaccharides (i.e., amylose and cellulose) and proteins (e.g., albumin, enzymes), among others. Only a handful of proteins have been investigated for use as HPLC CSPs despite their unique enantioselective properties. Unfortunately current, protein-based CSPs have low loading capacity, are expensive to prepare, and have limited stability. There is clearly a market need for enzyme and protein- based CSP separation methods with higher loading capacity, less degradation and extended shelf life. Based on market research interviews that we have conducted through NSF’s I-Corps program on our platform biomaterial technology, it was made clear that the technology for chiral columns has not changed and that innovation in the field was desired. Bondwell Technologies aims to develop a novel high-capacity protein-based selector for use as a CSP based on our innovative biomaterial. The unique qualities of our biomaterial addresses all of current limitations of chiral CBHs. During this proposed Phase I feasibility effort, we will first express the chiral selector enzyme cellobiohydrolase (CBH I) and form our biomaterials, We will test the enzyme in the biomaterial for function to ensure correct folding. We will then prepare our material to be used as a CSP. Finally, we will test for the ability of our biomaterial to separate enantiomers of the beta- bocking drugs, propranolol and alprenolol.