Synthesis of Highly Water-Soluble Adamantyl Phosphoinositide Derivatives

Abstract

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 facilitate future studies on the substrate specificities of these proteins involving cocrystallisation studies with proteins.

Sir John Cornforth Memorial Issue

“…[7] Andrew Holmes (the 2015 Cornforth Lecturer at The University of Sydney) and co-workers at The University of Melbourne and Oxford University report a synthesis of highly water-soluble adamantyl phosphoinositide derivatives. [8] Len Lindoy (The University of Sydney) with colleagues Jack Clegg at the University of Queensland, John McMurtrie at Queensland University of Technology, Kate Jolliffe at The University of Sydney, and Kerstin and Karsten Gloe at the Technische Universität Dresden describe selective solvent extraction of silver(I) by tris-pyridyl tripodal ligands, including an X-ray structure of a silver(I) coordination polymer incorporating one such ligand. [9] Chris McErlean (The University of Sydney) contributes a study on accessing brominated natural product motifs using phosphoramidate catalysis.…”