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 开发手性药物分离，分析和解决的方法的开发是 药物开发的重要兴趣。同一化合物的两个对映异构体可能 具有相同的物理或化学特性，但在它们相互作用的方式上显示出明显的差异 在人类系统中（即有关其药理学，毒理学，药代动力学和 代谢）。那就是药物的手性分离对于消除不必要的 制剂中的对映异构体。映异构体的分离通常是通过高位实现的 性能液相色谱（HPLC），其中手性选择器用于手性静止 阶段（CSP）。 CSP可以由几种类型的分子组成，包括多糖 （即，齐梅糖和纤维素）和蛋白质（例如白蛋白，酶）等。只有少数 已经研究了蛋白质的使用，就像HPLC CSP一样进行独特的对映选择性 特性。不幸的是，基于蛋白质的CSP的负载能力较低，很昂贵 准备并具有有限的稳定性。显然，市场需要酶和蛋白质 - 基于较高的加载能力，降低降低和扩展货架的基于CSP分离方法 生活。根据我们通过NSF的I-Corps计划进行的市场研究访谈 在我们的平台生物材料技术上，可以清楚地表明手性柱的技术 尚未改变，需要在现场进行创新。邦德威尔技术的目的是 基于我们的创新，开发出一种新型的高容量蛋白质选择器作为CSP用作CSP 生物材料。我们生物材料的独特品质解决了手性的所有当前局限性 CBHS。在此拟议的I阶段的可行性工作中，我们将首先表达手性选择器 酶纤维胞素水解酶（CBH I）并形成我们的生物材料，我们将测试该酶 生物材料的功能以确保正确折叠。然后，我们将准备我们的材料以用作 CSP。最后，我们将测试生物材料分离β-的对映异构体的能力 Bocking药物，普萘洛尔和alprenolol。