Facile Synthesis of Glycopolypeptides by Combination of Ring-Opening Polymerization of an Alkyne-Substituted N-carboxyanhydride and Click "Glycosylation"

Synthetic glycopolypeptides have attracted much interest for application in biomedical field as they are structural mimics to the natural glycopeptides or glycoproteins. However, the synthesis methods toward glycopolypeptides are still few or less efficient. Herein, we present a facile route to preparation of glycopolypeptides with highly effective “glycosylation” by click postpolymerization modification. First, an alkyne‐substituted N‐carboxyanhydride (NCA) monomer was synthesized and subsequently polymerized to afford the polypeptide with “clickable” alkyne pendants. The alkyne‐functionalized polypeptide was then “glycosylated” by click reaction of different sugar azides to the alkyne pendants with high efficiency. All the obtained glycopolypeptides were soluble and preferred α‐helix conformation in water. Primary studies on the obtained glycopolypeptides binding with Con A lectin were assessed by turbidimetric assay. The more quantitive studies of the interactions between lectin proteins and the synthetic glycopolypeptides, and the application of these materials as the multivalent ligands are in progress. An alkyne functional polypeptide poly(γ‐propargyl‐L‐glutamate) (PPLG) was synthesized and click “glycosylated” to prepare glycopolypeptides with diverse sugar residues. All the obtained glycopolypeptides adopted well‐defined α‐helix in water. Also, the versatile click method allowed us to prepare glycopolypeptides with various compositions of the sugar residues. The binding behaviors between the synthesized glycopolypeptides and model lectin Con A were assessed to be depending on the sugar compositions in the pendants.