Hsu Ku-Lung, Gildersleeve Jeffrey C, Mahal Lara K
Department of Chemistry and Biochemistry, University of Texas at Austin, 1 University Station, A5300, Austin, TX 78712-0265, USA.
Mol Biosyst. 2008 Jun;4(6):654-62. doi: 10.1039/b800725j. Epub 2008 Apr 14.
Glycomics, i.e. the high-throughput analysis of carbohydrates, has yet to reach the level of ease and import of its counterparts, genomics and proteomics, due to the difficulties inherent in carbohydrate analysis. The advent of lectin microarray technology addresses many of these problems, providing a straightforward approach for glycomic analysis. However, current microarrays are limited to the available lectin set, which consists mainly of plant lectins isolated from natural sources. These lectins have inherent problems including inconsistent activity and availability. Also, many plant lectins are glycosylated, complicating glycomic evaluation of complex samples, which may contain carbohydrate-binding proteins. The creation of a recombinant, well-defined lectin set would resolve many of these issues. Herein, we describe an efficient strategy for the systematic creation of recombinant lectins for use in microarray technology. We present a small panel of simple-to-purify bacterially-derived lectins that show reliable activity and define their binding specificities by both carbohydrate microarray and ELISA. We utilize this panel to create a recombinant lectin microarray that is able to distinguish glycopatterns for both proteins and cell samples. This work opens the door to the establishment of a vast set of defined lectins via high-throughout approaches, advancing lectin microarray technology for glycomic analysis.
糖组学,即对碳水化合物的高通量分析,由于碳水化合物分析中存在的固有困难,尚未达到其对应领域基因组学和蛋白质组学那样的便捷性和重要性水平。凝集素微阵列技术的出现解决了许多此类问题,为糖组学分析提供了一种直接的方法。然而,目前的微阵列仅限于现有的凝集素集合,该集合主要由从天然来源分离的植物凝集素组成。这些凝集素存在一些固有问题,包括活性不一致和可用性有限。此外,许多植物凝集素是糖基化的,这使得对可能含有碳水化合物结合蛋白的复杂样品进行糖组学评估变得复杂。创建一组重组的、定义明确的凝集素将解决许多此类问题。在此,我们描述了一种用于系统创建用于微阵列技术的重组凝集素的有效策略。我们展示了一小组易于纯化的细菌来源的凝集素,它们表现出可靠的活性,并通过碳水化合物微阵列和酶联免疫吸附测定法确定了它们的结合特异性。我们利用该组创建了一种重组凝集素微阵列,该微阵列能够区分蛋白质和细胞样品的糖型。这项工作为通过高通量方法建立大量定义明确的凝集素打开了大门,推动了用于糖组学分析的凝集素微阵列技术的发展。