Design, Synthesis, and Biological Evaluation of Ganglioside Hp-s1 Analogues Varying at Glucosyl Moiety.
Ganglioside Hp-s1 is isolated from the ovary of sea urchin Diadema setosum. It exhibited better neuritogenic activity than GM1 in pheochromocytoma 12 cells. To explore the roles of glucosyl moiety of Hp-s1 in contributing to the neurogenic activity, we developed feasible procedures for synthesis of Hp-s1 analogues (2a-2f). The glucosyl moiety of Hp-s1 was replaced with α-glucose, α-galactose, β-galactose, α-mannose, and β-mannose, and their biological activities on SH-SY5Y cells and natural killer T (NKT) cells were evaluated. We found that the orientation of C-2 hydroxyl group at glucosyl moiety of Hp-s1 plays an important role to induce neurite outgrowth of SH-SY5Y cells. Surprisingly, compound 2d could activate NKT cells to produce interleukin 2, although it did not show great activity on neurite outgrowth of SH-SY5Y cells. In general, the Hp-s1 might be considered as a lead compound for the development of novel drugs aimed at modulating the activity of neuronal cells.
Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou , Taoyuan 333, Taiwan.
Jung-Tung
JT
Hung
Department of Chemistry, National Chung Hsing University , Taichung 402, Taiwan.
Chun-Hong
CH
Yeh
Department of Chemistry, National Chung Hsing University , Taichung 402, Taiwan.
Shih-An
SA
Yang
Department of Chemistry, National Chung Hsing University , Taichung 402, Taiwan.
Chiu-Ya
CY
Lin
Department of Chemistry, National Chung Hsing University , Taichung 402, Taiwan.
Hung-Ju
HJ
Tai
Department of Chemistry, National Chung Hsing University , Taichung 402, Taiwan.
Ganesh B
GB
Shelke
Department of Chemistry, National Chung Hsing University , Taichung 402, Taiwan.
Daggula Mallikarjuna
DM
Reddy
Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou , Taoyuan 333, Taiwan.
Alice L
AL
Yu
Department of Chemistry, National Chung Hsing University , Taichung 402, Taiwan.
Shun-Yuan
SY
Luo
D000818:Animals; D002236:Carbohydrate Conformation; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D005677:G(M1) Ganglioside / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D008956:Models, Chemical; D015394:Molecular Structure; D016501:Neurites / Q000187:drug effects; D009447:Neuroblastoma; D055495:Neurogenesis / Q000187:drug effects*
D016207:Cytokines; D005677:G(M1) Ganglioside
Ganglioside Hp-s1; SH-SY5Y cells; glucosyl moiety of Hp-s1; neurogenic activity