Synthetic Strategies for Dynamic Covalent Protein Recognition

该项目将专注于构象预组织分子（拟肽折叠体）的设计和合成，这些分子可识别蛋白质表面的关键元素。这些支架将形成化学探针的工具包，以靶向：（i）蛋白质-蛋白质相互作用（PPI）和（ii）易于错误折叠的蛋白质。这些系统的异常控制是许多疾病的核心，如癌症，糖尿病和神经退行性疾病该项目的具体目标是：（i）设计、合成和表征新的肽模拟物折叠体;（ii）连接共价弹头，其可以选择性地与靶蛋白上的氨基侧链形成键;（iii）将共价弹头连接到靶蛋白上。（iii）研究它们介导治疗相关蛋白质行为的能力。

The project will focus on the design and synthesis of conformationally pre-organised molecules (peptidomimetic foldamers) that recognise key elements of protein surfaces. These scaffolds will form a toolkit of chemical probes to target: (i) protein-protein interactions (PPIs) and; (ii) proteins prone to misfolding. Aberrant control of these systems lies at the heart of many diseases such as cancer, diabetes and neurodegeneration (Alzheimer's, Parkinson's, and others).The Specific objectives of the project are the: (i) design, synthesis, and characterisation of new peptidomimetic foldamers; (ii) attachment of covalent warheads that can form bonds selectively with amino side-chains on the target protein; (iii) investigation of their ability to mediate the behaviour of therapeutically-relevant proteins.