Šunderić Miloš, Šedivá Alena, Robajac Dragana, Miljuš Goran, Gemeiner Peter, Nedić Olgica, Katrlík Jaroslav
Institute for the Application of Nuclear Energy, University of Belgrade, Belgrade, Serbia.
Institute of Chemistry, Slovak Academy of Sciences, Bratislava, Slovakia.
Biotechnol Appl Biochem. 2016 Jul;63(4):457-64. doi: 10.1002/bab.1407. Epub 2015 Aug 26.
Glycosylation is co- and posttranslational modifications affecting proteins. The glycopattern changes are associated with changes in biological function and are involved in many diseases including cancer. We present the lectin-based protein microarray method enabling determination of differences in protein glycosylation. The method involves isolation of targeted protein from samples by immunoprecipitation, spotting of protein from multiple samples into arrays on a microarray slide, incubation with set of biotinylated lectins, the reaction with fluorescent conjugate of streptavidin, and detection of fluorescent intensities by microarray scanner. Lectin-based protein microarray was applied in investigation of differences in alpha-2-macroglobulin (α2M) glycosylation isolated from sera samples of healthy persons and patients with colorectal cancer (CC). From 14 lectins used in analysis, statistically significant differences (Student's t-test, P < 0.05) between two groups of samples (persons without cancer and CC patients) were found for 5 of them. α2M molecules isolated from sera of CC patients have higher content of α2,6 sialic acid, N-acetylglucosamine and mannose residues, and tri-/tetraantennary complex type high-mannose N-glycans. A novel lectin-based protein microarray developed and described can serve as a suitable analytical technique for sensitive, simple, fast, and high-throughput determination of differences in protein glycosylation isolated from serum or other samples.
糖基化是影响蛋白质的共翻译和翻译后修饰。糖基模式的变化与生物学功能的改变相关,并涉及包括癌症在内的许多疾病。我们展示了基于凝集素的蛋白质微阵列方法,该方法能够确定蛋白质糖基化的差异。该方法包括通过免疫沉淀从样品中分离目标蛋白,将多个样品中的蛋白质点样到微阵列载玻片上的阵列中,与一组生物素化凝集素孵育,与链霉亲和素的荧光共轭物反应,以及通过微阵列扫描仪检测荧光强度。基于凝集素的蛋白质微阵列被应用于研究从健康人和结直肠癌(CC)患者血清样本中分离的α-2-巨球蛋白(α2M)糖基化的差异。在分析中使用的14种凝集素中,发现两组样品(无癌症患者和CC患者)之间有5种存在统计学显著差异(学生t检验,P < 0.05)。从CC患者血清中分离的α2M分子具有较高含量的α2,6唾液酸、N-乙酰葡糖胺和甘露糖残基,以及三/四天线复合型高甘露糖N-聚糖。所开发和描述的基于凝集素的新型蛋白质微阵列可作为一种合适的分析技术,用于灵敏、简单、快速和高通量地测定从血清或其他样品中分离的蛋白质糖基化差异。