Convergent Synthesis of Natural-Mimetic Glycerophospholipids: New Tools for Biological Studies and Cancer Cells Labelling

Glycerophosphlipids (GPLs) constitute the most important subclass of phospholipids. These biomolecules play multiple roles at the cellular level and are involved as major constituents in membrane bilayers, cellular compartmentalization and as intramolecular signaling molecules. We have recently demonstrated that, to preserve the native biological behavior of phosphatidic acids (PA, a GPL) probes, no modifications should be made to their fatty acid chains nor phosphate head, whereas only the addition of a clickable moiety on the glycerol backbone is acceptable. Since PA represent only a tiny fraction of GPLs, we have extended our synthetic methodology to more challenging families of GPLs such as phosphatidylethanolamine, phosphatidylcholine or phosphatidylserine by using an innovative and convergent approach. Moreover, the clickable moiety was used to allowed flexible grafting in cellulo of different molecules to GPLs analogues for various biological applications. This innovation thus provides powerful tools for selectively labeling cancer cells by exploiting the difference of composition of the membrane leaflets between normal and cancer cells.