Investigating the Role of N-Type Glycosylation in Protein-Ligand Interactions Using a Unique Commercial Microarray Technology

使用独特的商业微阵列技术研究 N 型糖基化在蛋白质-配体相互作用中的作用

• 批准号: 2493266
• 金额: --
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2493266
• 关键词: Investigating; Role; Type; Glycosylation; Protein

Over recent years microarray technology has been instrumental in expanding knowledge of the interactions between proteins and both synthetic and natural ligands, contributing to substantial advances in the global biopharmaceutical industry. Retrogenix Ltd. specialises in the production of unique cell microarrays, expressing thousands of full length human plasma membrane and secreted proteins. The advanced technology allows identification of interactions between proteins and potential ligands for biopharmaceutical clients. It is used for the discovery of novel therapeutics, identification of promising drug targets and safety assessment of drug candidates. There are a range of binding mechanisms and these can be affected by covalent modifications to the proteins, referred to as post-translational modifications. Glycosylation is the addition of glycans (sugars) to proteins and is the most complex post-translational modification of human proteins. Glycans affect protein structural and functional attributes including biological activity, half-life and cell targeting. It is a highly heterogenous process that is impacted by factors such as environmental conditions, and hence the manufacturing process would almost certainly affect the glycosylation profile of the membrane and secreted proteins. Hence, glycosylation could significantly impact on protein-ligand binding characteristics. This project aims to better understand how the process of sugar addition (N-glycosylation), affects both proteins and ligand interactions, and ultimately create a more diverse and powerful screen as well as helping to identify more "potent" cell interactions.

近年来，微阵列技术在扩大蛋白质与合成和天然配体之间相互作用的知识方面发挥了重要作用，为全球生物制药行业的实质性进步做出了贡献。Retrogenix有限公司专门生产独特的细胞微阵列，表达数千种全长的人类质膜和分泌蛋白。这项先进的技术可以为生物制药客户识别蛋白质和潜在配体之间的相互作用。它被用于发现新的治疗方法，识别有前景的药物靶点，以及对候选药物进行安全性评估。有一系列的结合机制，这些机制会受到蛋白质共价修饰的影响，这种修饰被称为翻译后修饰。糖基化是将糖链(糖)加到蛋白质上，是人类蛋白质最复杂的翻译后修饰。多糖影响蛋白质的结构和功能属性，包括生物活性、半衰期和细胞靶向性。这是一个高度异质性的过程，受到环境条件等因素的影响，因此制造过程几乎肯定会影响膜和分泌蛋白质的糖基化图谱。因此，糖基化可以显著影响蛋白质与配体的结合特性。该项目旨在更好地了解糖加成(N-糖基化)的过程如何影响蛋白质和配体的相互作用，并最终创建一个更多样化和更强大的筛查，以及帮助确定更“有效”的细胞相互作用。