Synthesis and biological evaluation of phosphatidylinositol phosphate affinity probes

SJ Conway; J Gardiner; SJA Grove; MK Johns; ZY Lim; GF Painter; DEJE Robinson; C Schieber; JW Thuring; LSM Wong; MX Yin; AW Burgess; B Catimel; PT Hawkins; NT Ktistakis; LR Stephens; AB Holmes

Journal article

Synthesis and biological evaluation of phosphatidylinositol phosphate affinity probes

SJ Conway, J Gardiner, SJA Grove, MK Johns, ZY Lim, GF Painter, DEJE Robinson, C Schieber, JW Thuring, LSM Wong, MX Yin, AW Burgess, B Catimel, PT Hawkins, NT Ktistakis, LR Stephens, AB Holmes

Organic and Biomolecular Chemistry | ROYAL SOC CHEMISTRY | Published : 2010

DOI: 10.1039/b913399b

Abstract

The synthesis of the complete family of phosphatidylinositol phosphate analogues (PIPs) from five key core intermediates A-E is described. These core compounds were obtained from myo-inositol orthoformate 1 via regioselective DIBAL-H and trimethylaluminium-mediated cleavages and a resolution-protection process using camphor acetals 10. Coupling of cores A-E with phosphoramidites 34 and 38, derived from the requisite protected lipid side chains, afforded the fully-protected PIPs. Removal of the remaining protecting groups was achieved via hydrogenolysis using palladium black or palladium hydroxide on carbon in the presence of sodium bicarbonate to afford the complete family of dipalmitoyl- an..

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University of Melbourne Researchers

Antony Burgess Author

Andrew Holmes Author

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Grants

Awarded by Australian Research Council, Discovery Project

Awarded by NHMRC

Awarded by Biotechnology and Biological Sciences Research Council

Awarded by Australian Research Council

Funding Acknowledgements

We thank the BBSRC and EPSRC for financial support and for provision of the Swansea Mass Spectrometry Service. This work was supported in part by the Australian Research Council, Discovery Project, Grant DP0770668 and an NHMRC Program Grant, 487922. General support was provided by CSIRO and VESKI (Victorian Endowment for Science, Knowledge and Innovation). We also thank Daiso Co., Ltd, Japan for the generous gift of (+)-1,2-O-isopropylidene-glycerol. SJC thanks Hughes Hall, Cambridge for a Research Fellowship. SJAG thanks GSK for a CASE studentship. Z-YL thanks Cambridge Commonwealth Trust, Universities UK (ORS award), New Hall, Cambridge and Tan Kar Kee Foundation, Singapore for generous financial support.