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 I期SBIR子序列标题为“液相色谱闪光灯 氧化（LC-FOX™）蛋白足迹系统，“对ackowed的反应 需要新的和改进的工具进行高阶结构分析（HOS） 生物制药。羟基自由基脚印（HRPF）是HOS分析技术 这涉及通过与羟基反应对蛋白质外部的不可逆标记 随后进行MS分析的自由基鉴定蛋白质的外部。什么时候 HRPF应用于动态变化的构象混合物，无法阐明 个别构象体。我们的LC-Fox蛋白足迹是一种新的台式方法 探针动态概念性异质混合物可以通过 各种形式的色谱法，包括尺寸排除（SEC），离子交换（IEX）， 和疏水相互作用色谱（HIC）。在第一阶段，我们将创建一个 原型系统要用等sec进行测试。 Gennext Technologies是唯一一家商业化技术的公司 HRPF HOS分析的产品。我们的总体目标是转换HRPF流程 从学术研究实验到广泛采用且宝贵的HOS 分析工具。我们的LC-Fox系统预计将对领域产生重大影响 生物制药研究 /开发，制定和药物输送，因为它将 启用不需要的构象体的检测和表征（潜力 在创建和引入新的情况下产生的不良药物反应） 生物治疗学。