We describe a process for engineering a synthetic polymer nanoparticle (NP) that functions as an effective, broad-spectrum metalloproteinase inhibitor. Inhibition is achieved by incorporating three functional elements in the NP; a group that interacts with the catalytic zinc ion, functionality that enhances affinity to the substrate-binding pocket and by fine-tuning the chemical composition of the polymer to strengthen NP affinity for the enzyme surface. The approach is validated by synthesis of a NP that sequesters and inhibits the proteolytic activity of snake venom metalloproteinases from five clinically relevant species of snakes. The mechanism of action of the NP mimics that of endog-enous tissue inhibitors of metalloproteinases. The strategy pro-vides a general design principle for synthesizing abiotic polymer inhibitors of enzymes.

中文翻译：

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金属蛋白酶内源性组织抑制剂的非生物模拟物。用作广谱金属蛋白酶抑制剂的工程合成聚合物纳米颗粒

我们描述了一种工程合成聚合物纳米颗粒 (NP) 的过程，该颗粒可作为有效的广谱金属蛋白酶抑制剂。抑制是通过在 NP 中加入三个功能元件来实现的；与催化锌离子相互作用的基团，增强对底物结合口袋的亲和力，并通过微调聚合物的化学成分以增强 NP 对酶表面的亲和力。该方法通过合成一种 NP 来验证，该 NP 可以隔离和抑制来自五种临床相关蛇种的蛇毒金属蛋白酶的蛋白水解活性。NP 的作用机制类似于金属蛋白酶的内源性组织抑制剂。该策略提供了合成酶的非生物聚合物抑制剂的一般设计原则。