Integrated Platform for Mass-Spectrometric Studies of Protein Structure

摘要 研究生物分子的高阶结构和相互作用的技术是一种 突出了NIGMS SBIR/STTR研究主题。研究用的质谱学方法 HOS包括羟基自由基足迹以及共价标记的化学方法 氨基酸侧链官能团，以及氢/氢交换(HDX) 蛋白质主链酰胺。这些方法只需要少量不一定纯净的 材料，可以研究蛋白质在溶液中的构象和动力学 配基。质谱学方法特别适合于生物药学的可比性 和表位图谱研究。目前，还没有能够分析质量的软件 来自共价标记和HDX实验的光谱数据，即使这两个 方法既有探针溶剂可及性，如果结合使用，将提供更好的分辨率和 更大的自信。结果将是供应商中立的商业软件，具有高级 可同时处理HDX和共价标记的分析和报告功能 实验。

Summary Technology for studying the higher order structure (HOS) and interactions of biomolecules is a highlighted NIGMS SBIR/STTR research topic. Mass-spectrometric methods for studying HOS include hydroxyl radical footprinting as well as chemical methods to covalently label amino acid side-chain functional groups, and also hydrogen/deuterium exchange (HDX) on protein backbone amides. These methods require only small amounts of not-necessarily-pure material, and can study conformation and dynamics of proteins in solution with or without ligands. Mass spectrometric methods are especially well suited to biopharma comparability and epitope mapping studies. Currently, there is no software that can analyze mass spectrometric data from both covalent labeling and HDX experiments, even though the two methods both probe solvent accessibility and, if combined, would give finer resolution and greater confidence. The outcome will be vendor-neutral commercial software with advanced analytical and reporting capabilities that can handle both HDX and covalent labeling experiments.