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

新型聚糖特异性试剂的开发和应用以促进早期诊断

• 批准号: 8728430
• 负责人: David C. Muddiman
• 金额: $ 5.21万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8728430
• 关键词: Address; Age; Age-Months; Animal Model; Animals; Biological; Biological Markers; Birds; Blood; CA-125 Antigen; Charge; Chemicals; Chemistry; Chickens; Cleaved cell; Collection; Communities; Complex Mixtures; Data; Detection; Development; Diagnosis; Diagnostic; Disease; Dissociation; ERBB2 gene; Early Diagnosis; Electrospray Ionization; Epithelial ovarian cancer; Evaluation; Foundations; Frequencies; Goals; Health; Heart Diseases; Homeostasis; Human; Immune System Diseases; Individual; Ions; Laboratory Study; Libraries; Link; Malignant Neoplasms; Mass Spectrum Analysis; Measurement; Measures; Methods; Modeling; Molecular; Molecular Weight; Pathology; Plasma; Plasma Proteins; Play; Polysaccharides; Population; Post-Translational Regulation; Prevalence; Prognostic Marker; Protein Glycosylation; Reagent; Reference Values; Regulation; Relative (related person); Research; Role; Sampling; Science; Solid; Stable Isotope Labeling; Staging; Structure; Survival Rate; Systems Biology; Techniques; Technology; Testing; Tissues; Translating; Up-Regulation; Update; Woman; analytical tool; anticancer research; base; biobank; cohort; comparative; design; improved; insight; instrumentation; ionization technique; mass analyzer; neurodevelopment; novel; open source; response; stable isotope; time interval; tool; user-friendly; web site

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.

描述（由申请人提供）：质谱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。质量分析仪技术，解离技术和电离方法的重大进展主要归因于质谱在系统生物学领域中扮演的核心作用。尽管在上个世纪中，质谱已演变为一种高效的分析工具，但仍有机会可以使新的进步允许解决各种各样的生物学问题。该建议集中在生物学质谱法新型聚糖特异性标签的发展和表征上，这些标签促进了从血浆蛋白裂解的相对定量，而离子丰度增加。该提案的短期目标是开发这些新型标签，然后使用自发上皮卵巢癌的鸟类模型对其进行测试。这些结果将提供一个可靠的生物分析技术基础，我们可以从中使用我们的新化学标签来实现有效阐明聚糖生物标志物的长期目标，以早日检测女性的上皮卵巢癌。对拟议研究质谱法（MS）的公众描述，与“称重分子”有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。但是，将利用用于基于MS的糖基质的前端化学成分，以显着提高MS检测和量化从血浆蛋白上裂解的糖的能力。这将允许解决各种各样的当代生物医学问题，包括量化诊断和预后生物标志物。该提案直接集中于阐明聚糖特异性生物标志物（S），以早日检测上皮卵巢癌。

项目成果

Hydrophobic derivatization of N-linked glycans for increased ion abundance in electrospray ionization mass spectrometry.

• DOI: 10.1007/s13361-011-0140-x
• 发表时间: 2011-08
• 期刊: JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
• 影响因子: 3.2
• 作者: Walker, S. Hunter;Lilley, Laura M.;Enamorado, Monica F.;Comins, Daniel L.;Muddiman, David C.
• 通讯作者: Muddiman, David C.

Interplay of permanent charge and hydrophobicity in the electrospray ionization of glycans.

• DOI: 10.1021/ac101227a
• 发表时间: 2010-08-01
• 期刊: Analytical chemistry
• 影响因子: 7.4
• 作者: Walker SH;Papas BN;Comins DL;Muddiman DC
• 通讯作者: Muddiman DC

The use of a xylosylated plant glycoprotein as an internal standard accounting for N-linked glycan cleavage and sample preparation variability.

使用木糖基化植物糖蛋白作为内标，解释 N-连接聚糖裂解和样品制备变异性。

• DOI: 10.1002/rcm.6579
• 发表时间: 2013
• 期刊: Rapid communications in mass spectrometry : RCM
• 作者: Walker,SHunter;Taylor,AmberD;Muddiman,DavidC
• 通讯作者: Muddiman,DavidC

Individuality Normalization when Labeling with Isotopic Glycan Hydrazide Tags (INLIGHT): a novel glycan-relative quantification strategy.

• DOI: 10.1007/s13361-013-0681-2
• 发表时间: 2013-09
• 期刊: JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
• 影响因子: 3.2
• 作者: Walker, S. Hunter;Taylor, Amber D.;Muddiman, David C.
• 通讯作者: Muddiman, David C.