Aryl transition metal chemical warheads for protein bioconjugation.
Aryl transition metal chemical warheads for protein bioconjugation.
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DOI：
10.1039/c8sc00780b
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发表时间：
2018-06-21
期刊：
影响因子：
8.4
通讯作者：
Blanchard N
中科院分区：
文献类型：
--
作者：
Bisseret P;Abdelkafi H;Blanchard N
使用芳基过渡金属试剂作为偶联伙伴的生物正交有机金属化学是一个新兴的领域，特别是在蛋白质研究方面具有很大的前景。在过去的七年里，蛋白质生物偶联反应蓬勃发展，突出了芳基过渡金属试剂作为偶联伙伴的作用。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，取代了平行开发的催化过程，已经能够在蛋白质底物上锻造C-S和C-C键，分别处于天然状态或配备预先安装的非天然末端烯烃或炔烃附件。虽然还没有应用于蛋白质，但指向C-N键的相关转化已经通过靶向多肽赖氨酸残基而被揭示。这项研究的核心是选择连接到过渡金属上的配体，以赋予金属配合物不仅在水介质中的稳定性，而且还具有所需的化学选择性。我们在这里总结这项工作，它已经使精致的钯和金络合物成为聚光灯下的焦点，这些络合物配备了生物相关的附件，如荧光和亲和标记，以及药物分子。这项研究不仅对蛋白质本身的研究很有希望，而且对设计新的基于蛋白质的生物疗法也很有希望，例如蛋白质-药物结合物或由大环化反应产生的限制性类似物。
Bioorthogonal organometallic chemistry using aryl transition metal reagents as coupling partners is a burgeoning field that holds great promise notably for the study of proteins. 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.
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