Synthesis of the essential core of the human glycosylphosphatidylinositol (GPI) anchor

The biological role of GPI anchors is of paramount importance; however, we are still far from fully understanding the structure–function relationship of these molecules. One major limiting factor has been the tiny quantities available from natural sources; obtaining homogeneous and well-defined GPI structures by synthesis, is both a challenge and an attractive goal. We report here the convergent synthesis of the essential core of the human GPI anchor 1, exploiting a common precursor to obtain the trisaccharidic donor 2 and a novel protecting groups sequence. The final product, prepared for the first time, is biologically active.

The first synthesis of the essential core of the human glycosylphosphatidylinositol (GPI) anchor is reported.Figure optionsDownload as PowerPoint slideResearch highlights
► The biological role of GPI anchors is of paramount importance.
► Obtaining by organic synthesis well-defined GPI structures is an attractive goal.
► Known synthesis of GPIs structure are not easily amenable to modifications.
► The final crucial step was optimized to give 1 suitable for biological tests.
► Preliminary biological tests indicate that our synthetic GPI is biologically active.