Merging Solid-Phase Peptide Synthesis and Automated Glycan Assembly to Prepare Lipid-Peptide-Glycan Chimeras

Biomaterials with improved biological features can be obtained by conjugating glycans to nanostructured peptides. Creating peptide-glycan chimeras requires superb chemoselectivity. We expedite access to such chimeras by merging peptide and glycan solid-phase syntheses employing a bifunctional monosaccharide. The concept was explored in the context of the on-resin generation of a model α(1→6)tetramannoside linked to peptides, lipids, steroids, and adamantane. Chimeras containing a β(1→6)tetraglucoside and self-assembling peptides such as FF, FFKLVFF, and the amphiphile palmitoyl-VVVAAAKKK were prepared in a fully automated manner. The robust synthetic protocol requires a single purification step to obtain overall yields of about 20 %. The β(1→6)tetraglucoside FFKLVFF chimera produces micelles rather than nanofibers formed by the peptide alone as judged by microscopy and circular dichroism. The peptide amphiphile-glycan chimera forms a disperse fiber network, creating opportunities for new glycan-based nanomaterials.