Selectivity phosphatidylinositol-3-kinases

The above-mentioned conditions were recently employed to perform a C5 arylation between 4-methyl-2-(Al-acetyl)aminothiazole and a 4-bromopyridine derivative (eq 28). The arylated thiazole thus obtained was used in the preparation of a selective phosphatidylinositol-3 kinase alpha-inhibitor. 

Okada, T. Sakuma, L. Fukui, Y Hazeki, O. Ui, M. Blockage of chemotactic peptide-induced stimulation of neutrophils by wortmannin as a result of selective inhibition of phosphatidylinositol 3-kinase. J. Biol. Chem., 269, 3563-3567 (1994)... 

T. Rahn, M. Ridderstrale, H. Tornqvist, V. Manganiello, G. Fredrikson, P. Belfrage, and E. Degerman, Essential role of phosphatidylinositol 3-kinase in insulin-induced activation and phosphorylation of the cGMP-inhibited cAMP phosphodiesterase in rat adipocytes studies using the selective inhibitor wortmannin, FEBS Lett., 1994, 350, 314-317. 

The number and breadth of reports of synthetic studies relating to phos-phatidylinositols and related structures has increased markedly as the following selection demonstrates. A series of unnatural phosphatidylinositols (41) with C2 to C18 fatty acids replacing the natural C20 fatty acid at the sn-2 position have been prepared and subjected to phosphorylation conditions with phos-phatidylinositol 3-kinase. The results show that phosphorylation can be achieved in molecules carrying small fatty acid side chains Cg shows reactivity comparable to that of the natural substrate. l-D-l-(sn-3-Phosphatidyl)-myo-inositol (42) has been prepared in excellent yield by the direct phosphatidylation of l-D-2,3,4,5,6-penta-0-benzyl-myo-inositol with sn-3-phosphatidic acid and subsequent deprotection (Scheme 6) The method has the advantage of producing products of unequivocal structure and stereochemical purity and being... 

This is still poorly understood. Proteins that bind to PI(3,4)P2 or Pl(3,4,5)Pj have PH domains (pleckstrin homology domains). One example of such a protein is protein kinase B PKB) this is activated by phosphorylation that is catalyzed by another PH domain kinase, PDKl (phosphatidylinositol-dependent kinase). Activated PKB phosphorylates a ribosomal protein, protein S6, which leads to increased rates of translation of selected mRNA molecules. 

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