Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Tianjin 300457, PR China.
School of Pharmaceutical Science, Shandong First Medical University & Shandong Academy of Medical Sciences, Tai'an, 271016, PR China.
Carbohydr Res. 2021 Nov;509:108431. doi: 10.1016/j.carres.2021.108431. Epub 2021 Sep 3.
A highly efficient chemoenzymatic method for synthesizing ganglioside GM3 and lyso-GM3 was reported here. Enzymatic extension of the chemically synthesized lactosyl sphingosine using efficient one-pot multienzyme (OPME) reaction allowed glycosylation to be carried out in aqueous solutions realizing the greening of reactions. Ganglioside GM3 was synthesized through 10 steps with a total yield of 22%. Lyso-GM3 was very useful for kinds of derivatization. The anti-proliferation activity studies demonstrated that these compounds 14-16 with sphingosine exhibited more potency than the corresponding lyso-GM3 with ceramide. All ganglioside GM3 and lyso-GM3 can effectively inhibit the migration of melanoma B16-F10 cells. These chemoenzymaticlly synthesized GM3 and lyso-GM3 exhibited antitumor activities, which can provide valuable sights to search new antitumor agents for cancer therapy.
本文报道了一种高效的化学酶法合成神经节苷脂 GM3 和溶酶体神经节苷脂 GM3 的方法。通过高效一锅多酶（OPME）反应，对化学合成的乳糖基神经鞘氨醇进行酶促延伸，使糖基化能够在水溶液中进行，实现了反应的绿色化。GM3 通过 10 步反应总收率为 22%合成。溶酶体神经节苷脂 GM3 非常适合进行各种衍生化。增殖活性研究表明，与相应的神经酰胺溶酶体 GM3 相比，具有神经鞘氨醇的化合物 14-16 具有更强的活性。所有神经节苷脂 GM3 和溶酶体神经节苷脂 GM3 均可有效抑制黑色素瘤 B16-F10 细胞的迁移。这些化学酶法合成的 GM3 和溶酶体神经节苷脂 GM3 表现出抗肿瘤活性，为寻找用于癌症治疗的新型抗肿瘤药物提供了有价值的思路。
