Synthesis of hybrid lipid probes: derivatives of phosphatidylethanolamine-extended phosphatidylinositol 4,5-bisphosphate (Pea-PIP(2)).
The total asymmetric synthesis of a novel hybrid lipid possessing a 2,3-diacylthreitol backbone, rather than a 1,2-diacylglycerol backbone, is described. The title compound, Pea-PIP(2), possesses a phosphatidylethanolamine (PE) headgroup at the 1-position and a phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)) headgroup at the 4-position. Reporters (biotin, fluorophores, spin label) were covalently attached to the free amino group of the PE, such that these reporters were targeted to the lipid-water interface. The diacyl moieties allow incorporation of Pea-PIP(2) into a lipid bilayer, while the PtdIns(4,5)P(2) moiety in the aqueous layer was specifically recognized by PtdIns(4,5)P(2)-specific binding proteins.
Rzepecki
Piotr W
PW
Department of Medicinal Chemistry, The University of Utah, 419 Wakara Way, Suite 205, Salt Lake City, Utah 84108, USA.
Prestwich
Glenn D
GD
D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D008968:Molecular Conformation; D015394:Molecular Structure; D010714:Phosphatidylethanolamines / Q000138:chemical synthesis* / Q000737:chemistry; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000138:chemical synthesis* / Q000737:chemistry
C465298:1-(4-(2-aminoethoxyphosphoryloxy)-2,3-di-O-palmitoylbutoxyphosphoryloxy)-4,5-inositolbisphosphate; D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D010714:Phosphatidylethanolamines; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols