Phosphatidylinositol analogues

The synthesis of the 2-deoxy phosphatidylinositol analogue 108 in which the phosphorus-containing group is introduced using a novel coupling agent, bis(diisopropylamino)(2-trimethylsilylethoxy)phosphine has been described. ... 

Hydrolytic cleavage by phosphatidylinositol phospholipase C (PI-PLC) of the cyclic myo-inositol-l,2-phosphate (cIP) at C-2 is faster than that at C-1. A cyclic monofluorophosphonate has been prepared as a stable analogue of the substrate in... 

Postulated transition state analogue Figure 7.63 Inhibition of phosphatidylinositol phospholipase C. 

Zhou, C., and Roberts, M.F., 1998, Nonessential activation and competitive inhibition of bacterial phosphatidylinositol-specific phospholipase C by short-chain phospholipids and analogues. Biochemistry 37 16430-16439. 

Williams SJ. Galactose-derived phosphonate analogues as potential inhibitors of phosphatidylinositol biosynthesis in mycobacteria. Org. Biomol. Chem. 2007 5 952-959. 132. 

The synthesis and biological activity of two new 3-hydroxy (phos-phono)methyl-bearing phosphatidylinositol ether lipid analogues (77) has been reported. These compounds are structurally related to PI-3-phosphate and act as reasonable good inhibitors of Akt and P13-K. They were also shown to inhibit the growth of HT-29 human colon cancer cells and MCF-7 human breast cancer cells. ... 

Vinod, T.K., Griffith. O.H., and Keana. J.F.W., Synthesis of isosteric and isopolar phosphonate subshate analogues designed as inhibitors for phosphatidylinositol-specific phosphohpase C from Bacillus cereus. Tetrahedron Lett., 35, 7193. 1994. 

Fluorinated Analogues of m> o-Inositols as Biological Probes of Phosphatidylinositol... 

Analogues of myo-lnositol were synthesized wherein certain hydroxyl groups were replaced with fluorine, and these were examined as substrates for phosphatidylinositol (Pl) synthetase. Fluorine substitution at the 2- and 4(6)-p03itions of myo-inositol (giving the acyllo- and myo-iaomers, respectively) resulted in loss of any detectable substrate activity. Replacement of the hydroxyl at C-5 of myo-inosltol resulted in retention of appreciable PI synthetase activity (ca. 2S% for the equatorial 5-deoxy-5-fluoro-myo- and ca. 1 (>% for the axially substituted 2-deoxy-2-fluoro-neo-inositol). 

The design and synthesis of phosphatidylinositol polyphosphates lipids (PIPn) headgroup scaffolds (69) from (68) that could be conveniently functionalized to obtain a number of derivatized analogues of use for different studies, have been presented by Best and co-workers (Scheme 13). ... 

Phosphatidylglycerol phosphate, 307, 505 diether analogue, 307 Phosphatidylinositol, 275,307, 507-08 aminoethyl phosphotriester isomer, synthesis, 307... 

Xu Y, Sculimbrene BR, Miller SJ (2006) Streamlined synthesis of phosphatidylinositol (PI), PI3P, PI3,5P2, and deoxygenated analogues as potential biological probes. J Org Chem 71 4919 928... 

A number of phosphorothioate and thiophosphate derivatives of myo- and cArro-inoatols have appeared. Thus, ID- and racemic- m inositol 1,4,5-trisphosphate 3-phosphorothioate, IL-m -inositol l,4,S-trisphosphorothioate, iL-cA/ro-inositol 1,4,6-tii o horothioate " and the thiophosphate analogue 130 of phosphatidylinositol have been described. 

A general approach to the synthesis of phosphorothioate, methylphosphonate and monofluromethylphosphonate analogues (19) of phosphatidylinositol-3-phosphate PtdIns(3)P have been also developed/ ... 

The first asymmetric synthesis of two phosphatidylinositol 3,4,5-triphosphate analogues (24) and (25) that are resistant to the 3-phosphatase PTEN and their biological activity, has been described. 

As5mimetric total S5mthesis of isosteric and isoelectronic phosphonate analogues (31)-(33) of phosphatidylinositol 4,5-phosphate, PtdIns(4,5)P2, that cannot be hydrolysed by phospholipase-C and their biological activity, has been described. A Pd(0) coupling not previously exploited in phospholipid or phosphoinositide synthesis was employed. It was also shown that a-fluorovinylphosphonate (32) optimally restored the sensitivity of the TRPM4 channel to... 

Berggren, MI, Gallegos, A, Dressier, LA, Modest, EJ and Powis, G (1993) Inhibition of the signalling enzyme phosphatidylinositol-3-kinase by antitumor ether hpid analogues. Cancer Res, 53,4297-4302. 

Powis, G, Seewald, Ml, Gratas, C, Melder, D, Riebow, J and Modest, El (1992) Selective inhibition of phosphatidylinositol phosphohpase C by cytotoxic ether lipid analogues. Cancer Res, 52, 2835-2840. 

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