一种化学酶级联策略,用于合成与结构多样化的FAHFA结合的酸丁胆
Oliver Bogojevic1, Yan Zhang1, Christian Daugaard Wolff1
1Department of Biological and Chemical Engineering, Faculty of Technical Sciences, Aarhus University, Gustav Wieds Vej 10, Aarhus 8000, Denmark.
The Journal of organic chemistry
|December 29, 2023
概括
对于糖尿病和炎症至关重要的基脂肪酸 (FAHFA) 的脂肪酸以一种新的化学酶法高效合成. 这种方法提高了这些有价值的脂质及其类型的可用性.
科学领域:
- 脂质化学 脂质化学
- 生物催化剂是一种生物催化剂.
- 药物发现 药物发现
背景情况:
- 基脂肪酸的脂肪酸 (FAHFA) 是内源性脂质,对糖尿病和炎症性疾病具有治疗潜力.
- 自然存在的FAHFA存在于非常低的度中,限制了它们的研究和应用.
研究的目的:
- 为各种FAHFA-脂物开发一种简单,可扩展和高度选择性的化学酶合成方法.
- 增加FAHFA的可用性,并为新型模拟开发提供工具.
主要方法:
- 不和脂肪酸以氧脂肪酸 (HFA) 的化.
- 使用Candida antarctica lipase A (CALA) 的脂肪酸对HFA进行酶性化.
- 基于carbodiimide的FAHFA与糖酸胆的结合.
主要成果:
- 在每个合成步骤中实现高产量 (74-98 mol %).
- 成功合成了一系列多样化的FAHFA类似物和FAHFA-脂.
- 确定了最佳反应条件,并通过分子对接评估了CALA基质亲和力.
结论:
- 化学酶方法为FAHFA生产提供了与传统化学合成相比的显著改进.
- 这一战略促进了FAHFA的生产,并使新型FAHFA结合物的产生成为可能,用于治疗研究.
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