Development of a Carbohydrate Microarray

癌细胞在疾病的发作和进展期间经历碳水化合物表达的急剧变化。不幸的是，人们对这些变化如何导致疾病知之甚少。此外，利用这些变化来开发诊断、肿瘤靶向剂或疫苗的努力只取得了有限的成功。其中一个关键的局限性是不能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固定在玻璃显微镜载玻片上的许多不同的碳水化合物抗原/表位。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。阵列的开发包括三个关键步骤：阵列的制造，评估结合的测定方法的开发，用于阵列的各种碳水化合物配体的化学合成，如碳水化合物肿瘤抗原，血型抗原和刘易斯抗原。我们已经成功地产生了碳水化合物微阵列和测定来检测结合。我们目前的微阵列包含92种不同的成分。我们将继续扩大和改进阵列。

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 92 different components. We will continue to expand and improve the array.