The development of retrosynthetic glycan libraries to profile and classify the human serum N-linked glycome.
The development of retrosynthetic glycan libraries to profile and classify the human serum N-linked glycome.
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DOI：
10.1002/pmic.200800760
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发表时间：
2009-06
期刊：
影响因子：
3.4
通讯作者：
Leiserowitz, Gary S.
中科院分区：
文献类型：
--
作者：
Kronewitter, Scott R.;An, Hyun Joo;de Leoz, Maria Lorna;Lebrilla, Carlito B.;Miyamoto, Suzanne;Leiserowitz, Gary S.
人血清N-连接糖组的注释是一个艰巨的挑战，但对于疾病标志物的发现是必要的。构建了一个新的理论聚糖库，并提出提供血清中所有可能的聚糖组成。它是基于已建立的糖生物学和逆合成状态转换网络开发的。我们发现，至少有331种组合物是可能的血清N-连接糖组。通过将理论聚糖质量库与高质量准确度和高分辨率质谱法配对，有效地分析了人血清聚糖。正确的同位素包络反褶积到单一同位素质量和高质量精度仪器大大减少了错误的组成分配的量。该文库的高通量能力允许对大的对照群体进行快速聚糖谱分析。使用该文库，从46名健康个体开发人血清聚糖质量谱。本文介绍了一个理论上的N-连接聚糖质量库，用于准确的高通量人血清聚糖谱。用于评估患者的糖组的快速方法对于研究基于聚糖的标志物是有用的。
Annotation of the human serum N-linked glycome is a formidable challenge but is necessary for disease marker discovery. A new theoretical glycan library was constructed and proposed to provide all possible glycan compositions in serum. It was developed based on established glycobiology and retrosynthetic state-transition networks. We find that at least 331 compositions are possible in the serum N-linked glycome. By pairing the theoretical glycan mass library with a high mass accuracy and high-resolution mass spectrometry, human serum glycans were effectively profiled. Correct isotopic envelope deconvolution to monoisotopic masses and the high mass accuracy instruments drastically reduced the amount of false composition assignments. The high throughput capacity enabled by this library permitted the rapid glycan profiling of large control populations. With the use of the library, a human serum glycan mass profile was developed from 46 healthy individuals. This paper presents a theoretical N-linked glycan mass library that was used for accurate high throughput human serum glycan profiling. Rapid methods for evaluating a patient’s glycome are instrumental for studying glycan based markers.
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