Copper-Containing Artificial Polyenzymes as a Clickase for Bioorthogonal Chemistry,Bioconjugate Chemistry

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Copper-Containing Artificial Polyenzymes as a Clickase for Bioorthogonal Chemistry
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2022-10-04 , DOI: 10.1021/acs.bioconjchem.2c00363
Ningning Zhang _{1,

2} , Patrick Bessel ₃ , Changzhu Wu _{4,

5}

Affiliation

Artificial polyenzymes (ArPoly) are tailored combinations of universal protein scaffolds and polymers newly proposed as promising alternatives to natural enzymes to expand the biocatalyst toolbox. The concept of ArPoly has been continuously extended to metal-containing ArPoly to overcome the drawbacks faced by conventional artificial metalloenzymes. Herein, we present a sustainable route to synthesize a novel water-soluble metalloenzyme for copper-catalyzed azide–alkyne cycloadditions in water with remarkable selectivity. In this case, synthetic l-proline monomers were polymerized onto bovine serum albumen in an aqueous medium via copper-mediated “grafting-from” atom-transfer radical polymerization, resulting in protein–polymer–copper conjugates named ArPoly_clickase. The copper in ArPoly_clickase plays pivotal bifunctional roles, not only as the catalyst for polymerization but also as the coordinated active site for alkyne–azide click catalysis. ArPoly_clickase showcases high efficiency, substrate generality, regioselectivity, and ease of product separation for “click chemistry” in water. Notably, ArPoly_clickase displays good biocompatibility without imposing copper toxicity on living cells, which offers the prospect for the upcoming bioorthogonal chemistry.

中文翻译：

含铜人工多酶作为生物正交化学的点击酶

人工多酶 (ArPoly) 是通用蛋白质支架和聚合物的定制组合，新近提出作为天然酶的有希望的替代品，以扩展生物催化剂工具箱。ArPoly 的概念不断扩展到含金属的 ArPoly，以克服传统人工金属酶所面临的缺点。在此，我们提出了一种可持续的途径来合成一种新型水溶性金属酶，用于水中铜催化的叠氮化物-炔烃环加成反应，具有显着的选择性。在这种情况下，合成的l-脯氨酸单体通过铜介导的“接枝自”原子转移自由基聚合反应在水性介质中聚合到牛血清蛋白上，产生名为 ArPoly _{clickase的蛋白质-聚合物-铜偶联物}. _ArPoly点击酶中的铜起着关键的双功能作用，不仅作为聚合催化剂，而且作为炔烃-叠氮化物点击催化的配位活性位点。ArPoly 点击_酶展示了水中“点击化学”的高效率、底物通用性、区域选择性和易于产品分离。值得注意的是，ArPoly _clickase显示出良好的生物相容性，不会对活细胞施加铜毒性，这为即将到来的生物正交化学提供了前景。

更新日期：2022-10-04

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