| Insulin is a hormone that plays a key role in glucose homeostasis by promoting the uptake of glucose and synthesis of lipids and glycogen in cells. The pathway by which the insulin signal is transduced inside an insulin-sensitive cell is very complex and many aspects of it are still not very well understood. It is believed that there is more than one possible signal transduction pathway and even several cross-talk mechanisms might exist between them. Inositol Phosphate Glycans (IPGs) are believed to be a class of compounds which act as second messengers in one of the less understood pathways of insulin signal transduction. They have also been shown to have significant insulin-mimetic properties when added exogenously to insulin-sensitive cells. Although these molecules are structurally similar to the glycosylphosphatidylinositol (GPI) membrane anchors, neither the exact chemical structures nor the mechanism of action are completely known yet. It has been shown that the presence of anionic groups on specific places in synthetic IPG analogs increases the insulin-mimetic properties of the compounds. However, the minimum structural requirement for an IPG to be significantly biologically active has not been established. Here, the synthesis of four anionic IPGs have been reported. Biological studies showed that all four of the compounds were significantly more active than their counterparts without the anionic group. Also, a much clearer structure-activity relationship for IPG molecules has emerged from these studies. These data will make the synthesis of active IPGs and mechanistic probes much simpler in the future. |
