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Inositolphosphoglycan Mediators Structurally Related to Glycosyl Phosphatidylinositol Anchors: Synthesis, Structure and Biological Activity
Author(s) -
MartínLomas Manuel,
Khiar Noureddine,
García Salud,
Koessler JeanLuc,
Nieto Pedro M.,
Rademacher Thomas W.
Publication year - 2000
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/1521-3765(20001002)6:19<3608::aid-chem3608>3.0.co;2-q
Subject(s) - inositol , phosphatidylinositol , glycosylation , biochemistry , chemistry , phosphatase , glycosyl , nuclear magnetic resonance spectroscopy , protein phosphatase 2 , stereochemistry , phosphorylation , receptor
The preparation of the pseudopentasaccharide 1 a , an inositolphosphoglycan (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 1 a to stimulate lipogenesis in rat adipocites as well as to inhibit cAMP dependent protein kinase and to activate pyruvate dehydrogenase phosphatase was investigated. Compound 1 a 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.