A Research Program on Advancing Biomedical Glycoproteomics

项目总结/摘要 蛋白质糖基化的疾病相关改变的生物医学相关性已被公认为 一段时间然而，在将这些观察结果转化为强有力的疾病方面仍然存在重大挑战。 生物标志物，并建立详细的分子理解如何改变蛋白质糖基化影响 多种多样的生物分子相互作用和蛋白质结构/功能相互作用。因为蛋白质 糖基化是复杂的非模板驱动的生物合成过程的最终结果， 对代谢异常异常非常敏感，包括伴随疾病的代谢异常。由于这些原因， 蛋白质糖基化的详细分子表征在生物医学领域具有很大的意义， 疾病生物标志物发现，以及用于关联疾病诱导的蛋白质糖基化改变的目的 to protein蛋白质function功能.这些努力的关键是强大的分析技术，可以确定 蛋白质连接聚糖的组成和结构及其在复合物中的蛋白质附着位点， 多相混合物此应用程序的MIRA计划要求支持的研究计划 致力于生物医学糖蛋白质组学的发展，应用， 传播基于质谱、串联质谱和离子迁移谱的工具， 询问糖蛋白质组并确定位点特异性蛋白质糖型。该计划的目标是 符合目前NIH的优先事项，包括最近呼吁增加早期投资， 生物医学研究新技术的开发和正在进行的促进以下方面进步的倡议： 糖科学这项工作将产生的新技术将是可推广的，因此适用于 在生物医学相关背景的折衷阵列中阐明位点特异性蛋白质糖型模式。

PROJECT SUMMARY / ABSTRACT The biomedical relevance of disease-related alterations in protein glycosylation has been recognized for some time. However, significant challenges remain in translating these observations into robust disease biomarkers, and in establishing a detailed molecular understanding of how altered protein glycosylation affects a diverse variety of biomolecular interactions and protein structure / function interplays. Because protein glycosylation is the end result of complex non-template-driven biosynthetic processes, a protein glycoform profile is exquisitely sensitive to metabolic irregularities, including those that accompany disease. For these reasons, the detailed molecular characterization of protein glycosylation is of great biomedical interest in the context of disease biomarker discovery, and for the purpose of relating disease-induced alterations of protein glycosylation to protein function. Essential to such endeavors are powerful analytical techniques that can determine the compositions and structures of protein-linked glycans and their sites of protein attachment in complex and heterogeneous mixtures. This application to the MIRA program requests support of a research program dedicated to the advancement of biomedical glycoproteomics through the development, application, and dissemination of mass spectrometry, tandem mass spectrometry, and ion mobility spectrometry based tools for interrogating the glycoproteome and determining site-specific protein glycoforms. The goals of this program are consonant with current NIH priorities, including the recent calls for increased investment in early stage development of new technologies for biomedical research and ongoing initiatives to catalyze advancements in glycoscience. The new technologies that will result from this work will be generalizable and thus applicable to the elucidation of site-specific protein glycoform patterns in an eclectic array of biomedically-relevant contexts.