The ability of natural metalloproteins to prevent inactivation of their metal cofactors by biological metabolites, such as glutathione, is an area that has been largely ignored in the field of artificial metalloenzyme (ArM) development. Yet, for ArM research to transition into future therapeutic applications, biocompatibility remains a crucial component. The work presented here shows the creation of a human serum albumin-based ArM that can robustly protect the catalytic activity of a bound ruthenium metal, even in the presence of 20 mM glutathione under in vitro conditions. To exploit this biocompatibility, the concept of glycosylated artificial metalloenzymes (GArM) was developed, which is based on functionalizing ArMs with N-glycan targeting moieties. As a potential drug therapy, this study shows that ruthenium-bound GArM complexes could preferentially accumulate to varying cancer cell lines via glycan-based targeting for prodrug activation of the anticancer agent umbelliprenin using ring-closing metathesis.

天然金属蛋白防止诸如谷胱甘肽之类的生物代谢物使其金属辅因子失活的能力是在人工金属酶（ArM）开发领域中被广泛忽略的领域。然而，对于ArM研究过渡到未来的治疗应用而言，生物相容性仍然是至关重要的组成部分。此处介绍的工作显示了基于人血清白蛋白的ArM的创建，即使在体外条件下存在20 mM谷胱甘肽的情况下，它也可以强有力地保护结合的钌金属的催化活性。为了利用这种生物相容性，开发了糖基化人工金属酶（GArM）的概念，该概念基于用N对ArM进行功能化-聚糖靶向部分。作为一种潜在的药物疗法，这项研究表明，钌结合的GArM复合物可以优先通过基于环的复分解的基于聚糖的靶向抗肿瘤药物伞形肾上腺素的前药活化而积累到各种癌细胞系中。