Makukhin Nikolai, Ciulli Alessio
Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee Dow Street DD1 5EH Dundee UK
RSC Med Chem. 2020 Oct 15;12(1):8-23. doi: 10.1039/d0md00272k.
Phosphotyrosine-containing compounds attract significant attention due to their potential to modulate signalling pathways by binding to phospho-writers, erasers and readers such as SH2 and PTB domain containing proteins. Phosphotyrosine derivatives provide useful chemical tools to study protein phosphorylation/dephosphorylation, and as such represent attractive starting points for the development of binding ligands and chemical probes to study biology, and for inhibitor and degrader drug design. To overcome enzymatic lability of the phosphate group, physiologically stable phosphonate-based phosphotyrosine analogues find utility in a wide range of applications. This review covers advances over the last decade in the design of phosphotyrosine and its phosphonate-based derivatives, highlights the improved and expanded synthetic toolbox, and illustrates applications in medicinal chemistry.
含磷酸酪氨酸的化合物因其能够通过与诸如含SH2和PTB结构域的蛋白质等磷酸化写入器、擦除器和读取器结合来调节信号通路而备受关注。磷酸酪氨酸衍生物为研究蛋白质磷酸化/去磷酸化提供了有用的化学工具，因此是开发用于研究生物学的结合配体和化学探针以及抑制剂和降解剂药物设计的有吸引力的起点。为了克服磷酸基团的酶促不稳定性，生理上稳定的基于膦酸酯的磷酸酪氨酸类似物在广泛的应用中得到了应用。本综述涵盖了过去十年中磷酸酪氨酸及其基于膦酸酯的衍生物设计方面的进展，突出了改进和扩展的合成工具箱，并阐述了其在药物化学中的应用。
