Modifications of peptides and proteins, primarily those found in chromatin, using metals such as palladium.

该项目的目的是使用钯介导的半胱氨酸生物缀合来产生具有乙酰赖氨酸模拟物的肽和重组蛋白。为了实现这一点，将使用稳定的金属络合物来选择性地官能化半胱氨酸残基，以基于S-CAr键形成产生新的侧链官能度。随后，将探索可以为溴结构域创建对接位点的修饰。溴结构域是在不同蛋白质上发现的小的相互作用模块，由此它们识别乙酰赖氨酸残基。它们在涉及多个治疗领域的信号传导过程中很重要，最常见的是在治疗肿瘤学中。纯化的溴结构域和我们的新乙酰赖氨酸模拟物之间的相互作用将使用生物化学和生物物理方法进行评估。如果成功，该项目将提供重要的（生物）化学工具，以推进溴结构域抑制剂的开发，并在药物发现中具有潜在的应用。

The aim of the project is to use palladium-mediated cysteine bioconjugation to generate peptides and recombinant proteins bearing acetyllysine mimics. To achieve this, stable metal complexes will be employed to selectively functionalise cysteine residues to generate new side-chain functionality based on S-CAr bond formation. Subsequently, modifications that can create docking sites for bromodomains will be explored. Bromodomains are small interaction modules found on diverse proteins whereby they recognise acetyllysine residues. They are important in signalling processes involved in several therapeutic areas, most commonly in therapeutic oncology. Interactions between purified bromodomains and our new acetyllysine mimics will be evaluated using biochemical and biophysical methods. If successful, this project will provide important (bio-)chemical tools to progress the development of bromodomain inhibitors with potential application in drug discovery.