Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, 741246, West Bengal, India.
Chembiochem. 2023 Jun 1;24(11):e202200758. doi: 10.1002/cbic.202200758. Epub 2023 May 4.
Glycosidases are a type of enzyme that hydrolytically cleave carbohydrates and form glycans for biologically important processes. The inadequacies of glycosidases or their genetic abnormalities are responsible for various diseases. Thus, the development of glycosidase mimetics is of great importance. We have designed and synthesized an enzyme mimetic containing l-phenylalanine, α-aminoisobutyric acid (Aib), l-leucine, and m-Nifedipine. From X-ray crystallography, the foldamer adopts a β-hairpin conformation stabilized by two 10-member and one 18-member NH⋅⋅⋅O=C hydrogen bonds. Moreover, the foldamer was found to be highly efficient in hydrolysing ethers and glycosides in the presence of iodine at room temperature. Further, X-ray analysis shows the backbone conformation of the enzyme mimetic to be almost unchanged after the glycosidase reaction. This is the first example of iodine-supported artificial glycosidase activity with an enzyme mimic at ambient conditions.
糖苷酶是一种能够水解碳水化合物并形成糖的酶，对于生物体内的重要过程具有重要意义。糖苷酶的不足或其遗传异常会导致各种疾病。因此，开发糖苷酶模拟物具有重要意义。我们设计并合成了一种包含 L-苯丙氨酸、α-氨基异丁酸（Aib）、L-亮氨酸和 m-硝苯地平的酶模拟物。通过 X 射线晶体学研究，该折叠体采用 β-发夹构象，由两个 10 元环和一个 18 元环的 NH⋅⋅⋅O=C 氢键稳定。此外，在室温下，碘存在时，该折叠体能高效水解醚和糖苷。进一步的 X 射线分析表明，酶模拟物在糖苷酶反应后其骨架构象几乎保持不变。这是首例在室温条件下，碘支持的人工糖苷酶活性的酶模拟物的例子。
