NIBRT Glycobiology Laboratory, NIBRT - The National Institute for Bioprocessing Research and Training, Fosters Avenue, Mount Merrion, Blackrock, Co Dublin, Ireland.
Glycoconj J. 2013 Feb;30(2):137-46. doi: 10.1007/s10719-012-9443-9. Epub 2012 Aug 26.
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.
许多翻译后修饰，包括糖基化，对于糖蛋白的结构完整性、位置和功能活性至关重要。通过这些修饰重新定位或功能改变的蛋白质亚群可以将静止蛋白转变为活性蛋白，从而介导特定的效应功能，如单克隆抗体。为了确保安全有效的药物，必须采用适当的稳健、定量分析策略，这些策略可以：(i) 进行详细的聚糖结构分析，(ii) 对特定的聚糖亚群进行特征描述，以评估治疗活性的已知关键特征，(iii) 快速分析聚糖池，用于在线监测或高水平的批间筛选。在这里，我们重点介绍糖基分析的这些方面，展示了在重组糖治疗药物生产的各个阶段都需要最先进的技术。这些数据可以深入了解加工途径，并为生物加工过程中的关键控制点以及患者疾病和药物监测中的关键决策点提供干预措施的标记物。重要的是，这些工具现在使人们能够在大人群中进行首次糖组/基因组研究，从而将糖组学整合到系统生物学背景下的其他“组学”平台中。
