Abstract:
Methodology for the efficient, automated and microwave-assisted Fmoc solid-phase synthesis of a 5(6)-carboxyfluorescein-labelled Lys(Dde)-Gly-Wang resin that can be further elongated through the lysine Nε amino group is described. Incorporation of O-dimannosylated peptides onto this resin using Fmoc-[α-D-Man(OBz)4-(1→6)-α-D-Man(OBz)3α1-]Ser-OH and PEG-[α-D-Man(OBz)4-(1→6)-α-D-Man(OBz)3α1-]-OH building blocks is demonstrated. Conditions were optimised to enable the efficient automated synthesis of several carboxyfluorescein-labelled dimannosylated peptides. 5(6)-Carboxyfluorescein was shown to be stable to the microwave conditions used for glycopeptide synthesis. The methodology described provides a robust, flexible synthetic platform for the preparation of a variety of fluorescently labelled glycopeptides (especially O-dimannosylated peptides) for biological evaluation.
