Multi-functionalization of helical block copoly(α-peptide)s by orthogonal chemistry

Diblock copoly(α-peptide)s bearing functional side-chains (i.e., azido or allyl) that are readily derivatized by “click” chemistry have been synthesized by primary amine-initiated sequential polymerization of the corresponding N-carboxyanhydrides (NCAs). Facile derivation of the side-chains has been demonstrated, in which mannose moieties are quantitatively attached via the alkyne–azide [2 + 3] Huisgen cycloaddition to form amphiphilic block copoly(α-peptide)s that retain their helical conformations in solution. Allyl side-chains residing in the hydrophobic core can be further functionalized with high efficiency by radical thiol–ene addition reactions despite the tendency of the amphiphilic precursors to aggregate.