Department of Chemistry, Indiana University, Bloomington, Indiana 47405, USA.
Dalton Trans. 2023 Apr 25;52(16):5034-5038. doi: 10.1039/d3dt00932g.
Artificial metalloenzymes (ArMs) can combine the unique features of both metal complexes and enzymes by incorporating a cofactor within a protein scaffold. Herein, we describe a panel of ArMs constructed by covalently linking Ir(III) polypyridyl complexes into a prolyl oligopeptidase scaffold. Spectroscopic methods were used to examine how properties of the resulting ArMs are influenced by structural variation of the cyclometalated ligands and the protein scaffold. Visible light photocatalysis by these hybrid catalysts was also examined, leading to the finding that they catalyze inter/intra-molecular [2 + 2] photocycloaddition in aqueous solution. Low but reproducible enantioselectivity was observed using a cofactor that undergoes partial kinetic resolution upon bioconjugation within the ArM active site, showing the importance of scaffold/cofactor interactions for enabling selective ArM photocatalysis. Further evidence of the importance of cofactor/scaffold interactions was provided by analyzing native POP peptidase catalysis by the ArMs. Together, these studies show how Ir(III)-based ArMs constitute a promising starting point for ongoing studies to control the stereoselectivity of EnT reactions by engineering substrate binding/activation motifs in POP.
人工金属酶（ArMs）可以通过将辅助因子结合到蛋白质支架中，结合金属配合物和酶的独特特性。在此，我们描述了一组通过将 Ir(III) 多吡啶配合物共价连接到脯氨酰寡肽酶支架中构建的 ArMs。光谱方法用于研究所得 ArMs 的性质如何受到金属化配体和蛋白质支架结构变化的影响。还检查了这些杂化催化剂的可见光光催化作用，发现它们在水溶液中催化分子间/分子内[2 + 2]光环加成反应。使用在 ArM 活性部位内进行部分动力学拆分的辅助因子观察到低但可重复的对映选择性，表明支架/辅助因子相互作用对于实现选择性 ArM 光催化的重要性。通过分析 ArMs 对天然 POP 肽酶的催化作用，提供了辅助因子/支架相互作用重要性的进一步证据。总之，这些研究表明基于 Ir(III) 的 ArMs 为通过工程化 POP 中底物结合/激活基序来控制 EnT 反应的立体选择性的持续研究提供了一个有希望的起点。
