Chemoenzymatic synthesis and biological evaluation of ganglioside GM3 and lyso-GM3 as potential agents for cancer therapy

  • Carbohydr Res. 2021 Nov:509:108431. doi: 10.1016/j.carres.2021.108431.
Tingshen Li  1 ,  Xiaodan Wang  2 ,  Peijie Dong  1 ,  Peng Yu  1 ,  Yongmin Zhang  3 ,  Xin Meng  4
Affiliations
  • 1. 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.
  • 2. School of Pharmaceutical Science, Shandong First Medical University & Shandong Academy of Medical Sciences, Tai'an, 271016, PR China.
  • 3. 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; Sorbonne Université, Institut Parisien de Chimie Moléculaire, UMR CNRS 8232, 4 Place Jussieu, 75005, Paris, France.
  • 4. 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. Electronic address: [email protected].
PMID: 34492428 DOI: 10.1016/j.carres.2021.108431
Abstract

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.

Keywords
Chemoenzymatic synthesis; Ganglioside GM3; Sialylation; Tumor-Associated Carbohydrate Antigens (TACAs).
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