Data di Pubblicazione:
2013
Citazione:
New sulfoglycophoshoramidates as phosphoinositide mimetics / L. Gabrielli, I. Calloni, M. Vetro, D. Colombo, D. Bini, B. Costa, L. Cipolla. ((Intervento presentato al 17. convegno European Carbohydrate Symposium tenutosi a Tel-Aviv nel 2013.
Abstract:
Protein kinases are enzymes involved in the regulation of many crucial cellular processes like proliferation, differentiation and apoptosis. Among them, the serine/threonine protein kinase B (PKB), also known as Akt, plays a key role as a component of the phosphoinositide 3-kinase (PI3K)-Akt-mTOR axis, which is implicated in aberrant tumor cell signaling. Inappropriate activation of the Akt kinase is a common event in human tumors and Akt is a critical player in cell survival. Thus, inhibitors that target PI3Ks and its downstream effectors, including PKB are potentially relevant for cancer therapy. PI3K activation generates 3-phosphorylated phosphatidylinositols [PI(3)P] that bind PKB pleckstrin homology (PH) domain promoting PKB activation through its translocation from the cytosol to the plasma membrane, conformational change and final phosphorylation. New glucose-based inositol analogues are currently investigated as potential Akt inhibitors and the structure of PI(3)P, natural ligand of PKB PH domain, can be easily reconducted to a suitably modified d-glucose scaffold as in phosphoramidate. Here, the synthesis of a set of unnatural sulphoglycophosphoramidate as PI(3)P analogues targeting the PKB PH domain will be reported. In particular, we synthesized a series of analogues of natural sulfoquinovosylacylglycerols (SQAG) in which sulfoquinovose is beta-linked to a phosphoramidate moiety with different alkyl chains.
Tipologia IRIS:
14 - Intervento a convegno non pubblicato
Keywords:
Protein kinase; PKB; phosphatidylinositols; pleckstrin homology domain; tumor; phosphoramidate
Elenco autori:
L. Gabrielli, I. Calloni, M. Vetro, D. Colombo, D. Bini, B. Costa, L. Cipolla
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