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

Tingshen Li (1) , Xiaodan Wang (2) , Peijie Dong (1) , Peng Yu (1) , Yongmin Zhang (3, 1) , Xin Meng (1)

1 TUST - Tianjin University of Science and Technology
2 SDAS - Shandong Academy of Sciences
3 IPCM - Institut Parisien de Chimie Moléculaire

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.

Mots clés: Chemoenzymatic synthesis; Ganglioside GM3; Sialylation; Tumor-Associated Carbohydrate Antigens (TACAs)

Domaines: Biochimie, Biologie Moléculaire

Tingshen Li, Xiaodan Wang, Peijie Dong, Peng Yu, Yongmin Zhang, et al.. Chemoenzymatic synthesis and biological evaluation of ganglioside GM3 and lyso-GM3 as potential agents for cancer therapy. Carbohydrate Research, 2021, 509, pp.108431. ⟨10.1016/j.carres.2021.108431⟩. ⟨hal-03359520⟩