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 Phase I SBIR提交的标题为“液相色谱快速 氧化（LC-Fox™）蛋白质足迹系统”是对已知的 需要新的和改进的工具，用于高阶结构分析（HOS）， 生物制药羟基自由基足迹法（HRPF）是一种HOS分析技术 通过与羟基反应， 随后进行MS分析以鉴定蛋白质的外部部分。当 应用于动态变化的构象混合物，HRPF未能阐明 单个构象异构体。我们的LC-Fox蛋白质足迹法是一种新的台式方法， 探针动态构象异构混合物，可通过 各种形式的层析，包括尺寸排阻（SEC），离子交换（IEX）， 和疏水性相互作用色谱法（HIC）。在第一阶段，我们将创建一个 用等度SEC测试原型系统。 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。我们的首要目标是将HRPF流程 从一个学术研究实验转变为一个被广泛采用的有价值的居屋计划 分析工具。我们的LC-Fox系统预计将在以下领域产生重大影响 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（和潜在的构象）， 药物不良反应）的发生和引入新的 生物治疗