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在药物发现中使用P450酶进行后期功能化

Vincent Poon¹, Christopher Bailey², Sandra Carvalho³

¹Hypha Discovery Limited, 154B Brook Drive, Milton Park, Abingdon OX14 4SD, U.K.

Journal of medicinal chemistry

|October 12, 2025

概括

酶套件使药物发现的后期氧化能够有效地进行. 这种方法加速了生物活性化合物的合成和选,节省了时间和资源.

科学领域:

生物催化和药物发现
酶合成酶的合成
药用化学医学化学

背景情况:

复杂分子的化学合成,特别是用于药物发现,可能是耗时和资源密集的.
晚期功能化是药物化学中的一个关键瓶.
酶方法为向分子修改提供了一个有希望的替代方案.

研究的目的:

为了证明商用酶基套件 (PolyCYPs选套件) 在生物相关化合物的后期基化中的实用性.
与传统化学合成相比,评估酶生物转换的效率.
评估酶合成化合物对各种病原体的生物活性.

主要方法:

使用商业可用的酶套件进行晚期氧化.
扩大了有前途的生物转化和分离/阐明的产品结构.
对病原体进行查的分离化合物包括*Schistosoma mansoni*,*Leishmania donovani*,*Trypanosoma cruzi*和*Trypanosoma brucei*.

主要成果:

使用酶套件成功实现了生物相关化合物的后期氧化.
与化学合成相比,已证明有效地生成用于生物查的数据.
扩大了打击化合物的生产规模,以便进一步调查.
在比标准合成化学更少的步骤中实现了化合物的生物合成合成.

结论:

使用PolyCYPs等套件的酶性基化提供了一条高效,更快速的途径到生物活性化合物.
这种方法显著减少了对广泛合成化学的需求,节省了药物发现计划中的时间和资源.
酶方法的可扩展性允许快速访问化合物,以便进一步研究和开发.

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