Strategies for the profiling, characterisation and detailed structural analysis of N-linked oligosaccharides
Strategies for the profiling, characterisation and detailed structural analysis of N-linked oligosaccharides
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DOI：
10.1007/s10719-012-9443-9
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发表时间：
2013-02
影响因子：
3
通讯作者：
T. Tharmalingam;B. Adamczyk;M. Doherty;L. Royle;P. Rudd
中科院分区：
文献类型：
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作者：
T. Tharmalingam;B. Adamczyk;M. Doherty;L. Royle;P. Rudd
许多翻译后修饰，包括糖基化，对糖蛋白的结构完整性、定位和功能活性至关重要。通过这种修饰重新定位或功能改变的蛋白质亚群可以将静止蛋白改变为活性蛋白，介导特定的效应功能，如单克隆抗体。为了确保药物的安全和有效，必须采用适当的强大的定量分析策略，可以(i)执行详细的聚糖结构分析，（ii）表征特定的聚糖亚群，以评估已知的治疗活性的关键特征，（iii）快速分析用于在线监测或高水平批量筛选的聚糖池。在这里，我们将重点关注聚糖分析的这些方面，展示在重组糖疗法生产的各个阶段如何需要最先进的技术。这些数据可以提供对加工途径的见解，并建议在生物加工的关键控制点进行干预的标记，以及在患者疾病和药物监测的关键决策点。重要的是，这些工具现在能够在大量人群中进行首次糖组学/基因组研究，允许糖组学在系统生物学背景下整合到其他组学平台中。
Many post-translational modifications, including glycosylation, are pivotal for the structural integrity, location and functional activity of glycoproteins. Sub-populations of proteins that are relocated or functionally changed by such modifications can change resting proteins into active ones, mediating specific effector functions, as in the case of monoclonal antibodies. To ensure safe and efficacious drugs it is essential to employ appropriate robust, quantitative analytical strategies that can (i) perform detailed glycan structural analysis, (ii) characterise specific subsets of glycans to assess known critical features of therapeutic activities (iii) rapidly profile glycan pools for at-line monitoring or high level batch to batch screening. Here we focus on these aspects of glycan analysis, showing how state-of-the-art technologies are required at all stages during the production of recombinant glycotherapeutics. These data can provide insights into processing pathways and suggest markers for intervention at critical control points in bioprocessing and also critical decision points in disease and drug monitoring in patients. Importantly, these tools are now enabling the first glycome/genome studies in large populations, allowing the integration of glycomics into other ‘omics platforms in a systems biology context.