Development of a Carbohydrate Microarray

在疾病的发生和发展过程中，癌细胞的碳水化合物表达发生了巨大的变化。不幸的是，人们对这些变化是如何导致这种疾病的知之甚少。此外，利用这些变化开发诊断、肿瘤靶向药物或疫苗的努力只取得了有限的成功。其中一个关键的限制是无法快速和全面地评估碳水化合物-蛋白质相互作用的特异性。我们正在开发一种碳水化合物微阵列来解决这个问题。碳水化合物微阵列包含许多不同的碳水化合物抗原/表位固定在玻璃显微镜载玻片上。使用阵列，可以快速分析抗体、凝集素、病毒、毒素或细胞与许多不同的潜在碳水化合物配体的结合。该阵列的开发包括三个关键步骤：阵列的制造，开发一种评估结合的方法，化学合成广泛的碳水化合物配体，如碳水化合物肿瘤抗原，血型抗原和阵列的lewis抗原。我们已经成功地生成了一个碳水化合物微阵列和检测结合的方法。我们目前的微阵列包含107个不同的组件。我们将继续扩大和完善该阵列。

Cancer cells undergo dramatic changes in carbohydrate expression during the onset and progression of disease. Unfortunately, little is known about how these changes contribute to the disease. Moreover, efforts to exploit these changes for the development of diagnostics, tumor targeting agents, or vaccines have had only limited success. One of the key limitations is the inability to evaluate the specificity of carbohydrate-protein interactions in a rapid and comprehensive manor. We are developing a carbohydrate microarray to address this issue. A carbohydrate microarray contains many different carbohydrate antigens/epitopes immobilized onto a glass microscope slide. Using an array, one can quickly analyze binding of antibodies, lectins, viruses, toxins, or cells to many different potential carbohydrate ligands simultaneously. Development of the array involved three key steps: fabrication of the arrays, development of an assay to evaluate binding, chemical synthesis of a broad range of carbohydrate ligands such as carbohydrate tumor antigens, blood group antigens, and lewis antigens for the array. We have successfully generated a carbohydrate microarray and assay to detect binding. Our current generation microarray contains 107 different components. We will continue to expand and improve the array.