Azobenzenes are of particular interest as a photochromic scaffold for biological applications because of their high fatigue resistance, their large geometrical change between extended (trans) and bent (cis) isomer, and their diverse synthetic accessibility. Despite their wide-spread use, there is no reported photochromic inhibitor of the well-investigated enzyme β-galactosidase, which plays an important role for biochemistry and single molecule studies. Herein, we report the synthesis of photochromic competitive β-galactosidase inhibitors based on the molecular structure of 2-phenylethyl β-D-thiogalactoside (PETG) and 1-amino-1-deoxy-β-D-galactose (β-D-galactosylamine). The thermally highly stable PETG-based azobenzenes show excellent photochromic properties in polar solvents and moderate to high photostationary states (PSS). The optimized compound 37 is a strong competitive inhibitior of β-galactosidase from Escherichia coli and its inhibition constant (K_i) changes between 60 nM and 290 nM upon irradiation with light. Additional docking experiments supported the observed structure–activity relationship.

中文翻译：

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β-半乳糖苷酶光开关抑制剂的开发

偶氮苯作为生物应用的光致变色支架尤为受关注，因为它们具有较高的抗疲劳性，在扩展的（反式）和弯曲的（顺式）异构体之间存在较大的几何变化，并且具有多种合成途径。尽管已广泛使用它们，但尚无报道对酶β-半乳糖苷酶的光致变色抑制剂进行研究，该酶在生物化学和单分子研究中起着重要作用。在这里，我们报告基于2-苯基乙基β- D-硫代半乳糖苷（PETG）和1-氨基-1-脱氧-β - D-半乳糖（β- D）的分子结构合成光致变色竞争性β-半乳糖苷酶抑制剂-半乳糖胺）。具有高度热稳定性的基于PETG的偶氮苯在极性溶剂中显示出出色的光致变色特性，并具有中等至高的光平稳态（PSS）。优化的化合物37是来自大肠杆菌的强竞争性β-半乳糖苷酶的抑制剂，并且在光照射下其抑制常数（K _i）在60nM至290nM之间变化。额外的对接实验支持观察到的结构-活性关系。