Development and Application of Novel Glycan-Specific Reagents to Facilitate Early

描述(申请人提供)：质谱仪是一种非常强大的生物分析技术，对我们对人类健康和疾病的分子理解产生了深远的影响。质谱仪技术、解离技术和电离方法的重大进步在很大程度上归功于质谱学在系统生物学领域中发挥的核心作用。虽然质谱学在上个世纪已经发展成为一种高效的分析工具，但仍有机会取得新的进展，从而解决更多样化的生物学问题。这项建议的核心是开发和表征用于生物质谱学的新的糖链特异性标记，以促进从离子丰度增加的血浆蛋白中切割出的糖链的相对定量。这项提议的短期目标是开发这些新的标签，然后使用自发性卵巢上皮癌的禽类模型来测试它们。这些结果将提供坚实的生物分析技术基础，我们新开发的化学标签可以应用于实现有效阐明用于女性上皮性卵巢癌早期检测的葡聚糖生物标志物的长期目标。公开描述研究质谱学(MS)是一门与“分子重量”相关的科学，对人类健康和疾病的研究产生了深远的影响，包括癌症、心脏病、神经发育和自身免疫性疾病。然而，基于MS的糖组分的前端化学将被利用来显著提高MS检测和定量从血浆蛋白质中切割出的多糖的能力。这将使更多样化的当代生物医学问题得到解决，包括对诊断和预后生物标记物的量化。这项建议完全集中在阐明一种糖链特异的生物标记物(S)用于卵巢上皮癌的早期检测。

DESCRIPTION (provided by applicant): Mass spectrometry is an extraordinarily powerful bio-analytical technique that has had a profound impact on our molecular understanding of human health and disease. Major advances in mass analyzer technology, dissociation techniques, and ionization methods are largely attributed to the central role that mass spectrometry plays in the field of systems biology. While mass spectrometry has evolved over the last century into a highly effective analytical tool, there are still opportunities for new advances to be made allowing an even more diverse array of biological questions to be addressed. This proposal is centered on the development and characterization of novel glycan- specific tags for biological mass spectrometry that facilitate the relative quantification of glycans cleaved from plasma proteins with increased ion abundance. The short-term objective of this proposal is to develop these novel tags and then test them using the avian model of spontaneous epithelial ovarian cancer. These results will provide a solid bio-analytical technology foundation from which our newly developed chemical tags can be applied to achieve the long-term objective of effectively elucidating glycan biomarkers for the early detection of epithelial ovarian cancer in women. Public Description of Proposed Research Mass spectrometry (MS), the science related to the "weighing of molecules", has had a profound impact on the study of human health and disease including cancer, heart disease, neural development, and auto-immune diseases. However, front-end chemistries for MS-based glycomics will be exploited to dramatically improve the ability of MS to detect and quantify glycans cleaved from plasma proteins. This will allow a more diverse array of contemporary biomedical questions to be addressed including the quantification of diagnostic and prognostic biomarkers. This proposal is squarely centered on the elucidation of a glycan-specific biomarker(s) for the early detection of epithelial ovarian cancer.