STRUCTURE-ACTIVITY RELATIONSHIP OF SYNTHETIC PHOSPHOINOSITOLGLYCANS MIMICKING METABOLIC INSULIN ACTION

Phosphoinositolglycan (PIG) molecules have been implicated to stimulate glucose and lipid metabolism in insulin-sensitive cells and tissues in vitro and in vivo. The structural requirements for this partial insulin-mimetic activity remained unclear so far. For establishment of a first structure−activity relationship, a number of PIG compounds were synthesized consisting of the complete or shortened/mutated glycan moiety derived from the structure of the glycosylphosphatidylinositol (GPI) anchor of the GPI-anchored protein, Gce1p, from yeast. The PIG compounds were divided into four classes according to their insulin-mimetic activity in vitro with the typical representatives:  compound 41, HO-SO2-O-6Manα1(Manα1-2)-2Manα1(6-HSO3)-6Manα1-4GluNβ1-6(d)inositol-1,2-(cyclic)-phosphate; compound 37, HO-PO(H)O-6Manα1(Manα1-2)-2Manα1-6Manα1-4GluNβ1-6(d)inositol-1,2-(cyclic)-phosphate; compound 7, HO-PO(H)O-6Manα1-4GluN(1-6(l)inositol-1,2-(cyclic)-phosphate; and compound 1, HO-PO(H)O-6Manα1-4GluN(1-6(l)inositol. Com...