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

描述（由申请人提供）：质谱法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。质量分析技术、解离技术和电离方法的重大进展主要归功于质谱在系统生物学领域中的核心作用。虽然质谱在上个世纪已经发展成为一种非常有效的分析工具，但仍然有机会取得新的进展，从而可以解决更多样化的生物学问题。该提案集中于开发和表征用于生物质谱的新型聚糖特异性标签，其促进从具有增加的离子丰度的血浆蛋白裂解的聚糖的相对定量。这项提案的短期目标是开发这些新的标签，然后使用自发性上皮性卵巢癌的禽类模型对其进行测试。这些结果将为我们新开发的化学标签提供坚实的生物分析技术基础，以实现有效阐明聚糖生物标志物的长期目标，从而早期检测女性上皮性卵巢癌。质谱（MS）是一门与“分子称重”相关的科学，对人类健康和疾病（包括癌症、心脏病、神经发育和自身免疫疾病）的研究产生了深远的影响。然而，基于MS的糖组学的前端化学将被利用，以显着提高MS检测和定量从血浆蛋白裂解的聚糖的能力。这将允许更多样化的当代生物医学问题得到解决，包括诊断和预后生物标志物的量化。该提案的核心是阐明用于早期检测上皮性卵巢癌的聚糖特异性生物标志物。

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.