Exploring the therapeutic potential of chimeric proteins

探索嵌合蛋白的治疗潜力

• 批准号: 1947736
• 金额: --
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1947736
• 关键词: Exploring; therapeutic; potential; chimeric; proteins

This projects aims to design and evolve proteases with therapeutic potential following a new conceptual approach, in which separate binding and catalytic domains are covalenty combined in chimeric 'captivases'. This will overcome the difficulty of engineering both binding and catalytic functions in one active site, instead relying on modular design principles. Starting points for this effort are one one hand existing antibodies (to provide binding) and on the other the catalytic potential of proteases with promiscuous activities (see 'Combinatorial Screening Identifies Novel Promiscuous Matrix Metalloproteinase Activities That Lead to Inhibition of the Therapeutic Target IL-13; C. Urbach, et al. & F Hollfelder, and L Jermutus; Chemistry & Biology (2015), 22(11):1442-52). Later such constructs will be evolved (see ChemBioChem.doi: 10.1002/cbic.201500295 - and using ultrahigh-throughput screening in microfluidic droplets - see Nature Communications 2015, 6:10008- DOI: 10.1038/ncomms10008), mechanistically characterised and improved and then tested on medically relevant targets (with collaborators at MedImmune).

该项目旨在设计和进化具有治疗潜力的蛋白酶，遵循一种新的概念方法，其中分离的结合和催化结构域在嵌合的“俘获酶”中共价结合。这将克服在一个活性位点上同时具有结合和催化功能的工程困难，而不是依赖于模块化设计原则。这项工作的出发点一方面是现有的抗体（提供结合），另一方面是具有混杂活性的蛋白酶的催化潜力(参见“组合筛选鉴定导致抑制治疗靶点IL-13的新型混杂基质金属蛋白酶活性；C. Urbach等人；F Hollfelder和L Jermutus； Chemistry & Biology（2015), 22(11):1442-52）。以后这样的结构将进化（见化学生物化学）。doi: 10.1002 / cbic。201500295 -并在微流控液滴中使用超高通量筛选-见Nature Communications 2015,6:10008- DOI: 10.1038/ncomms10008)，机械表征和改进，然后在医学相关目标上进行测试（与MedImmune的合作者）。

项目成果

Methods to Study Antigen-Specific B cells

研究抗原特异性 B 细胞的方法

• DOI: 10.17863/cam.90159
• 发表时间: 2021
• 作者: Fischer K