Institute for Molecular Engineering , The University of Chicago , Chicago , Illinois 60637 , United States.
J Am Chem Soc. 2019 Jun 19;141(24):9693-9700. doi: 10.1021/jacs.9b04181. Epub 2019 Jun 4.
Recent work has shown that polymeric catalysts can mimic some of the remarkable features of metalloenzymes by binding substrates in proximity to a bound metal center. We report here an unexpected role for the polymer: multivalent, reversible, and adaptive binding to protein surfaces allowing for accelerated catalytic modification of proteins. The catalysts studied are a group of copper-containing single-chain polymeric nanoparticles (Cu-SCNP) that exhibit enzyme-like catalysis of the copper-mediated azide-alkyne cycloaddition reaction. The Cu-SCNP use a previously observed "uptake mode", binding small-molecule alkynes and azides inside a water-soluble amphiphilic polymer and proximal to copper catalytic sites, but with unprecedented rates. Remarkably, a combined experimental and computational study shows that the same Cu-SCNP perform a more efficient click reaction on modified protein surfaces and cell surface glycans than do small-molecule catalysts. The catalysis occurs through an "attach mode" where the SCNPs reversibly bind protein surfaces through multiple hydrophobic and electrostatic contacts. The results more broadly point to a wider capability for polymeric catalysts as artificial metalloenzymes, especially as it relates to bioapplications.
最近的研究表明，聚合催化剂可以通过将底物与结合的金属中心附近的结合来模拟金属酶的一些显著特征。我们在这里报告了聚合物的一个意外作用：多价、可逆和自适应结合蛋白质表面，从而加速蛋白质的催化修饰。所研究的催化剂是一组含有铜的单链聚合纳米颗粒（Cu-SCNP），它们表现出类似于酶的铜介导的叠氮化物-炔烃环加成反应的催化作用。Cu-SCNP 使用先前观察到的“摄取模式”，在水溶性两亲聚合物内部结合小分子炔烃和叠氮化物，并靠近铜催化位点，但具有前所未有的速率。值得注意的是，一项综合实验和计算研究表明，相同的 Cu-SCNP 在修饰的蛋白质表面和细胞表面糖上进行更有效的点击反应，比小分子催化剂更有效。这种催化作用是通过“附着模式”发生的，其中 SCNP 通过多个疏水和静电接触可逆地结合蛋白质表面。这些结果更广泛地指出了聚合催化剂作为人工金属酶的更广泛的能力，特别是在涉及生物应用的方面。
