Novel biomaterial for enantiomer separation

用于对映体分离的新型生物材料

• 批准号: 10385251
• 负责人: Christi Parham
• 金额: $ 27.58万
• 依托单位: BONDWELL TECHNOLOGIES LP
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-04 至 2024-05-03
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10385251
• 关键词: Address; Aging; Air; Albumins; Alprenolol; Amylose; Behavior; Binding; Biocompatible Materials; Buffers; Cellulose; Characteristics; Chimeric Proteins; Column Chromatography; Consumption; Cryopreservation; Development; Drosophila Proteins; Drug Kinetics; Electrospinning; Ensure; Enzyme Tests; Enzymes; Feasibility Studies; Fiber; Film; High Pressure Liquid Chromatography; Housing; Human; Human body; Humidifier; Innovation Corps; Interview; Life; Market Research; Mechanics; Membrane; Metabolism; Methods; Molecular Biology Techniques; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology and Toxicology; Phase; Polysaccharides; Preparation; Process; Property; Propranolol; Proteins; Recipe; Resolution; Silicon Dioxide; Specificity; Syringes; System; Technology; Temperature; Testing; Therapeutic; Time; Viscosity; Water; Work; base; chemical property; cost; covalent bond; crosslink; dityrosine; enantiomer; enzyme activity; experimental study; innovation; interest; medication safety; method development; monomer; novel; physical property; programs; protein purification; success

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.

项目摘要 手性药物的分离、分析和拆分方法的发展， 对药物开发具有重要意义。同一化合物的两种对映体可以 具有相同的物理或化学性质，但在相互作用方面存在显著差异 在人类系统中（即，关于其药理学、毒理学、药代动力学和 代谢）。因此，药物的手性分离对于消除不需要的杂质是重要的。 对映异构体。对映异构体的分离通常通过高- 高效液相色谱法（HPLC），其中手性选择剂用于手性固定相 阶段（CSP）。CSP可以由几种类型的分子组成，包括多糖 (i.e.,直链淀粉和纤维素）和蛋白质（例如，白蛋白、酶）等。只有少数 尽管蛋白质具有独特的对映选择性， 特性.不幸的是，目前，基于蛋白质的CSP具有低负载能力， 稳定性有限。很明显市场需要酶和蛋白质- 基于CSP的分离方法，具有更高的装载能力，更少的退化和扩展的货架 生活根据我们通过NSF的I-Corps计划进行的市场调查访谈， 在我们的生物材料技术平台上，很明显， 这一点没有改变，需要在该领域进行创新。Bondwell Technologies致力于 开发一种新型的高容量基于蛋白质的选择器，用作CSP，基于我们的创新 生物材料我们的生物材料的独特品质解决了目前手性药物的所有局限性， CBH在这个提议的第一阶段可行性工作中，我们将首先表达手性选择剂 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，以确保正确的折叠。然后，我们将准备我们的材料， 一个CSP最后，我们将测试我们的生物材料分离β-内酰胺酶对映体的能力， 兴奋剂普萘洛尔和阿普洛尔