Department of Chemistry, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA.
Bioorg Med Chem Lett. 2011 Sep 1;21(17):4945-50. doi: 10.1016/j.bmcl.2011.05.045. Epub 2011 May 18.
Most clinically approved biomarkers of cancer are glycoproteins, and those residing on the cell surface are of particular interest in biotherapeutics. We report a method for selective labeling, affinity enrichment, and identification of cell-surface glycoproteins. PC-3 cells and primary human prostate cancer tissue were treated with peracetylated N-azidoacetylgalactosamine, resulting in metabolic labeling of cell surface glycans with the azidosugar. We used mass spectrometry to identify over 70 cell surface glycoproteins and biochemically validated CD146 and integrin beta-4, both of which are known to promote metastatic behavior. These results establish cell-surface glycoproteomics as an effective technique for discovery of cancer biomarkers.
大多数经临床认可的癌症生物标志物为糖蛋白,而那些位于细胞表面的糖蛋白在生物治疗中特别受到关注。我们报告了一种选择性标记、亲和富集和鉴定细胞表面糖蛋白的方法。PC-3 细胞和原发性人前列腺癌组织用乙酰化 N-叠氮乙酰半乳糖胺处理,导致细胞表面聚糖用叠氮糖进行代谢标记。我们使用质谱法鉴定了超过 70 种细胞表面糖蛋白,并通过生物化学方法验证了 CD146 和整合素β-4,这两者都已知能促进转移行为。这些结果确立了细胞表面糖蛋白质组学作为发现癌症生物标志物的有效技术。