Liquid Chromatography Flash Oxidation (LC-Fox™) Protein Footprinting System

液相色谱闪蒸氧化 (LC-Fox™) 蛋白质足迹系统

• 批准号: 10698726
• 负责人: Scot Randy Weinberger
• 金额: $ 35万
• 依托单位: GENNEXT TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2024-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10698726
• 关键词: Address; Adopted; Adoption; Appearance; Area; Award; Behavior; Biological; Biological Process; Biological Products; Biological Response Modifier Therapy; Chromatography; Companions; Comparative Study; Compensation; Computer software; Crystallization; Crystallography; Dangerousness; Data; Data Analyses; Detection; Development; Drug Delivery Systems; Environment; Exclusion; Feedback; Formulation; Goals; Heat-Shock Response; Heterogeneity; Higher Order Chromatin Structure; Hydrophobic Interactions; Hydroxyl Radical; Immune response; Individual; Ion Exchange; Label; Lasers; Letters; Light; Link; Liquid Chromatography; Manuals; Marketing; Methods; Modernization; Molecular Conformation; National Institute of General Medical Sciences; Nature; Patients; Pharmacologic Substance; Pharmacology; Phase; Play; Post-Translational Protein Processing; Process; Production; Protein Conformation; Protein Footprinting; Proteins; Proteomics; Reaction; Reporting; Research; Research Personnel; Resolution; Role; Safety; Sampling; Signal Transduction; Small Business Innovation Research Grant; Solvents; Source; Structure; System; Techniques; Technology; Testing; Time; adalimumab; adverse drug reaction; analytical tool; biopharmaceutical industry; commercialization; conformer; dosimetry; dynamic system; experimental study; improved; instrument; interest; new technology; novel; operation; oxidation; prevent; programs; prototype; research and development; therapeutic protein; tool

The GenNext Phase I SBIR submssion entitled “Liquid Chromatography Flash Oxidation (LC-Fox™) Protein Footprinting System,” is responsive to the ackowledged need for new and improved tools for higher order structural analysis (HOS) of biopharmaceuticals. Hydroxyl radical foot-printing (HRPF) is a HOS analytical technique that involves the irreversible labeling of a protein’s exterior by reaction with hydroxyl radicals with subsequent MS analysis to identify the outer portions of the protein. When applied to dynamically changing mixtures of conformation, HRPF fails to elucidate individual conformers. Our LC-Fox Protein Footprinting is a new, bench-top method to probe dynamic conformational heterogeneous mixtures that can be separated via various forms of chromatography, including size exclusion (SEC), ion exchange (IEX), and hydrophobic interaction chromatography (HIC). In Phase I we will create a prototype system to be tested with isocratic SEC. GenNext Technologies is the only company commercializing technology and products for HRPF HOS analysis. Our overarching goal is to convert the HRPF process from an academic research experiment into a broadly adopted and valuable HOS analytical tool. Our LC-Fox system is predicted to make substantial impact in the field of biopharmaceutical research / development, formulation, and drug delivery, as it will enable the detection and characterization of unwanted conformers (and potential adverse drug reactions) created during the genesis and introduction of new biotherapeutics.

GenNext 第一阶段 SBIR 提交的题为“Liquid Chromatography Flash 氧化 (LC-Fox™) 蛋白质足迹系统”是对公认的 需要新的和改进的工具来进行高阶结构分析（HOS） 羟基自由基足迹 (HRPF) 是一种 HOS 分析技术。 涉及通过与羟基反应对蛋白质外部进行不可逆标记 自由基和随后的 MS 分析来识别蛋白质的外部部分。 应用于动态变化的构象混合物，HRPF 未能阐明 我们的 LC-Fox 蛋白质足迹分析是一种新的台式方法。 探针动态构象异质混合物，可以通过 各种形式的色谱法，包括尺寸排阻 (SEC)、离子交换 (IEX)、 在第一阶段，我们将创建一个疏水相互作用色谱（HIC）。 原型系统将使用等度 SEC 进行测试。 GenNext Technologies 是唯一一家将技术商业化的公司 用于 HRPF HOS 分析的产品 我们的首要目标是转换 HRPF 流程。 从学术研究实验到广泛采用且有价值的居屋 我们的 LC-Fox 系统预计将在该领域产生重大影响。 生物制药研究/开发、配方和药物输送，因为它将 能够检测和表征不需要的构象异构体（以及潜在的 药物不良反应）在新药物的产生和引入过程中产生 生物治疗学。