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

Abstract

AbstractBiomaterials 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.