Journal article

Synthesis of Highly Water-Soluble Adamantyl Phosphoinositide Derivatives

Mark Gregory, Meng-Xin Yin, Malcolm J McConville, Eleanor Williams, Alex N Bullock, Stuart J Conway, Antony W Burgess, Bruno Catimel, Andrew B Holmes

Australian Journal of Chemistry | CSIRO PUBLISHING | Published : 2015


Phosphatidylinositol phosphates are key regulators of cell signalling pathways and membrane trafficking in eukaryotic cells, and there is a need for new chemical probes to further understand how they interact with lipid-binding proteins. Here, the synthesis of phosphatidylinositol phosphate analogues containing adamantyl carboxylic ester groups, in place of the natural lipid side chains, is described. These derivatives are considerably more soluble in water than analogues containing other lipid side chains and do not form large aggregates such as liposomes or micelles. These adamantyl analogues bind to known phosphoinositide-binding proteins with similar affinities to native ligands and will..

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Awarded by Australian Research Council

Awarded by Wellcome Trust

Funding Acknowledgements

We thank the Australian Research Council for supporting this work through Discovery Project (DP1094497). We would also like to thank The University of Melbourne, Bio21 Institute, Agilent Technologies, and the Newton Abraham Trust (Oxford) for financial support. MJM is a National Health and Medical Research Council (NHMRC) Principal Research Fellow. The Structural Genomics Consortium(SGC) is a registered charity (no. 1097737) that receives funds from AbbVie, Bayer Pharma AG, Boehringer Ingelheim, the Canada Foundation for Innovation, Genome Canada, GlaxoSmithKline, Janssen, Lilly Canada, the Novartis Research Foundation, the Ontario Ministry of Economic Development and Innovation, Pfizer, Takeda, and the Wellcome Trust (grant no. 092809/Z/10/Z).