Inositolphosphoglycan mediators structurally related to glycosyl phosphatidylinositol anchors: synthesis, structure and biological activity.
The preparation of the pseudopentasaccharide 1a, an inositol-phosphoglycan (IPG) that contains the conserved linear structure of glycosyl phosphatidylinositol anchors (GPI anchors), was carried out by using a highly convergent 2+3-block synthesis approach which involves imidate and sulfoxide glycosylation reactions. The preferred solution conformation of this structure was determined by using NMR spectroscopy and molecular dynamics simulations prior to carrying out quantitative structure--activity relationship studies in connection with the insulin signalling process. The ability of 1a to stimulate lipogenesis in rat adipocytes as well as to inhibit cAMP dependent protein kinase and to activate pyruvate dehydrogenase phosphatase was investigated. Compound 1a did not show any significant activity, which may be taken as a strong indication that the GPI anchors are not the precursors of the IPG mediators.
Martín-Lomas
M
M
Grupo de Carbohidratos, Instituto de Investigaciones Químicas CSIC-UNSE, Sevilla, Spain. manuel.martin-lomas@iiq.cartuja.csic.es
Khiar
N
N
García
S
S
Koessler
J L
JL
Nieto
P M
PM
Rademacher
T W
TW
D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D018360:Crystallography, X-Ray; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017261:Glycosylphosphatidylinositols / Q000737:chemistry*; D007295:Inositol Phosphates; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011134:Polysaccharides; D051381:Rats; D014346:Trypanosoma brucei brucei / Q000378:metabolism
D004791:Enzyme Inhibitors; D017261:Glycosylphosphatidylinositols; D007295:Inositol Phosphates; D009844:Oligosaccharides; D011134:Polysaccharides; C028039:inositol phosphate glycan; D017868:Cyclic AMP-Dependent Protein Kinases