The past seven years have witnessed the burgeoning of protein bioconjugation reactions highlighting aryl transition metal reagents as coupling partners. This new bioorthogonal organometallic chemistry, which sets the scene for stoichiometric processes in place of the catalytic procedures that developed in parallel, already enabled the forging of C–S and C–C bonds onto protein substrates, respectively in their native state or equipped with pre-installed non-natural terminal alkene or alkyne appendages. Although not yet applied to proteins, related transformations pointing to the creation of C–N bonds have, in addition, just been disclosed by targeting peptide lysine residues. Central to this research was the selection of ligands attached to the transition metal, in order to confer to metal complexes, not only their stability in aqueous medium, but also the desired chemoselectivity. We summarize here this body of work, which has already put in the limelight elaborated palladium and gold complexes equipped with biologically relevant appendages, such as fluorescent and affinity tags, as well as drug molecules. This research holds much promise, not only for the study of proteins themselves, but also for the design of new protein-based biotherapeutics, such as protein-drug conjugates or constrained analogs resulting from macrocyclisation reactions.

中文翻译：

---

用于蛋白质生物缀合的芳基过渡金属化学战斗部

在过去的七年中，蛋白质生物共轭反应迅速发展，突出了芳基过渡金属试剂作为偶联伴侣的重要性。这种新的生物正交有机金属化学为化学计量过程奠定了基础，取代了并行开发的催化程序，已经使C–S和C–C键能够分别在其天然状态或配备有前体的情况下在蛋白质底物上锻造。 -安装的非天然末端烯烃或炔烃附件。尽管尚未应用于蛋白质，但指向肽赖氨酸残基的研究还表明了指向C–N键的相关转化。这项研究的中心是选择与过渡金属相连的配体，以便赋予金属络合物，不仅是它们在水性介质中的稳定性，而且还具有所需的化学选择性。我们在这里总结了这一工作成果，该工作成果已成为备受瞩目的精制钯和金配合物，并配备了与生物有关的附属物，例如荧光和亲和标签以及药物分子。这项研究不仅在蛋白质本身的研究上，而且在设计新的基于蛋白质的生物疗法（例如蛋白质-药物结合物或大环化反应产生的受约束的类似物）方面，都具有广阔的前景。