MATRIX-ASSISTED LASER DESORPTION--FUNDAMENTAL STUDIES

描述：基质辅助激光解吸/电离(MALDI) 近年来，质谱学已经成为一种强大的新资源 生物医学研究人员。应用于分析范围广泛的 生物分子的重要类别，包括蛋白质、多肽、单抗 抗体、寡核苷酸和糖蛋白尤其 令人印象深刻。MALDI涉及的基本机制的基础研究 仍然需要提高对解吸的基本理解 进程本身。这些研究有望扩大 该技术并在分子质量等方面提供了改进 与生物相关的准确度、灵敏度和质量分辨率 材料。最近的结果是基于不断演变的模型 解吸/电离过程已将其用途扩展到简单的 分子量测定。亚稳离子衰变产物产生于 MALDI在提供多肽和序列信息方面非常有用 一些蛋白质。与传统方法相比的优势包括速度 分析和高灵敏度(皮摩尔)的方法。这样的能力 为生化研究人员提供了新的机遇。 提出了各种基础研究，以改善这两个基础 理解亚稳态离子衰变过程并探索分析 由多肽和蛋白质产生的序列离子的用途。 建议对现有仪器进行改进，以允许系统地 影响短期和长期的实验参数的研究 亚稳态衰变过程在飞行时间质谱仪中的重要作用 (TOF-MS)。这类研究也可能有助于MALDI TOF-MS的使用 用于更灵活的生化系统的技术，如更大的 寡核苷酸。亚稳衰变过程似乎是一个限制因素 在较大的寡核苷酸可以获得的质量分辨率中。 将MALDI技术扩展到包括中红外激光解吸 (2.8µm)可以允许更多的生物相容的基质 待利用(冷冻缓冲水溶液)。这种方法可以允许 非共价分子相互作用(三级结构) MALDI工艺。这将开辟一系列重要的生物学 用于质谱学研究的系统。此外，基本因素 将探索对电离过程重要的可能导致新的 这项技术的应用领域和现有技术的改进 方法论。

DESCRIPTION: Matrix-assisted laser desorption/ionization (MALDI) coupled to mass spectrometry has emerged in recent years as a powerful new resource for the biomedical researcher. Applications to the analysis of a wide range of important classes of biomolecules, including proteins, peptides, monoclonal antibodies, oligonucleotides and glycoproteins have been particularly impressive. Basic Studies of the fundamental mechanism involved in MALDI are still required to improved the basic understanding of the desorption process itself. These studies are expected to expand the applicability of the technique and provide improvements in such areas as molecular mass accuracy, sensitivity and mass resolution for biologically relevant materials. Recent results based upon the continually evolving models of the desorption/ionization process have expanded its utility beyond simple molecular weight determinations. Metastable ion decay products produced in MALDI are very useful in providing sequence information for peptides and some proteins. Advantages over conventional approaches include the speed of analysis and high sensitivity (picomoles) of the method. Such capabilities offer new opportunities for the biochemical researcher. A variety of basic studies are proposed to improve both the fundamental understanding of the metastable ion decay process and explore the analytical utility of the sequence ions produced from peptides and proteins. Improvements to existing instrumentation are proposed to allow a systematic study of the experimental parameters affecting both the short and long term metastable decay process important in time-of-flight mass spectrometry (TOF-MS). Such studies might also assist in the utility of the MALDI TOF-MS technique for more facile biochemical systems such as larger oligonucleotides. Metastable decay process appear to be a limiting factor in the mass resolution which can be obtained for larger oligonucleotides. Extension of the MALDI technique to include mid-infrared laser desorption (2.8 mu m) is proposed which may allow more biologically compatible matrices to be utilized (frozen buffered aqueous solutions). This approach may allow noncovalent molecular interactions (tertiary structures) to survive the MALDI process. This would open up a wide range of important biological systems for study by mass spectrometry. In addition, basic factors important to the ionization process will be explored that could lead to new application areas for this technique and to improvements in existing methodology.