Design, Synthesis, and Biological Evaluation of Ganglioside Hp-s1 Analogues Varying at Glucosyl Moiety

Abstract

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.

Ganglioside Hp-s1 Analogue Inhibits Amyloidogenic Toxicity in Alzheimer’s Disease Model Cells

“…Hp-s1 and Hp-s1A have only two saccharide bases. Replacing the glycosyl moiety reduces the neuritogenic activities of Hp-s1 . The saccharide portion of a ganglioside may play an important role in the interaction with hydrophilic regions of a protein or other molecules.…”

“…Replacing the glycosyl moiety reduces the neuritogenic activities of Hp-s1. 28 The saccharide portion of a ganglioside may play an important role in the interaction with hydrophilic regions of a protein or other molecules. In addition to the saccharide composition, the ceramide structures in these gangliosides are also different.…”

Chemistry and Biology of Bioactive Glycolipids of Marine Origin

“…The same authors carried out an SAR study involving the synthesis of six Hp-s1 analogues ( 156 – 161 ) by replacing the glucosyl unit of Hp-s1 with α-glucose ( 157 ), α- and β-galactose ( 158 and 159 ), and α- and β-mannose ( 160 and 161 ), including the simple cerebroside 156 [ 66 ]. After the biological evaluation, the authors found that the C-2 hydroxyl group of the glucosyl unit played a crucial role in the stimulation of neurite outgrowth of SH-SY5Y cells.…”

Mild and Highly α‐Selective O‐Sialylation Method Based on Pre‐Activation: Access to Gangliosides Hp‐s1, DSG‐A, and Their Analogues

“…[11] Recently,w ep ublished the ganglioside Hp-s1 and its derivatives for the study of neurological efficacy. [12] Am onomethylated ganglioside, DSG-A,w as isolated from the ovary of the sea urchin Diademas etosum and reported by Highuchie tal. [13] Tsai and co-workers published the first synthesis of ganglioside DSG-A.…”