Bisseret Philippe, Abdelkafi Hajer, Blanchard Nicolas
Université de Haute-Alsace , Université de Strasbourg , CNRS , LIMA , UMR 7042 , 68000 Mulhouse , France . https://bsm.unistra.fr ; Email:
Chem Sci. 2018 May 23;9(23):5132-5144. doi: 10.1039/c8sc00780b. eCollection 2018 Jun 21.
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.
在过去的七年里，蛋白质生物共轭反应蓬勃发展，其中芳基过渡金属试剂作为偶联伙伴备受关注。这种新型的生物正交有机金属化学为化学计量过程奠定了基础，取代了与之并行发展的催化过程，已经能够分别在天然状态或配备有预先安装的非天然末端烯烃或炔烃附属物的蛋白质底物上形成C-S键和C-C键。此外，尽管尚未应用于蛋白质，但针对肽赖氨酸残基的相关转化刚刚被披露，这些转化指向C-N键的形成。这项研究的核心是选择与过渡金属相连的配体，以便赋予金属配合物在水性介质中的稳定性以及所需的化学选择性。我们在此总结这一系列工作，这些工作已经使配备有生物相关附属物（如荧光和亲和标签以及药物分子）的精心设计的钯和金配合物成为焦点。这项研究不仅对蛋白质本身的研究有很大的前景，而且对新型蛋白质基生物治疗药物的设计也有很大前景，例如蛋白质-药物缀合物或大环化反应产生的受限类似物。
