Clickable, Oxidation-Responsive and Enzyme-Degradable Polypeptide: Synthesis, Characterization and Side Chain Modification

Modifications at polypeptide side chains have been found to affect conformational and properties, which is a vital strategy to prepare functional polypeptides. This contribution describes the synthesis of homo and co-polypeptides containing unsaturated bonds and thioether moieties, poly( S -allylcysteine) (PAC). The pendant vinyl groups provide an active binding site which are able to be further modified with cysteine by thiol-ene click reaction. The sulfoxide from thioether oxidation bestows the polypeptide water solubility and enzymatic catalytic sites. The self-assembly micelles of PEG- b -PAC are ruptured along with oxidation to release the Nile red payloads. Moreover, poly( S -allyl-cysteine sulfoxide), aka. polyalliin, is the oxidation product of PAC which undergoes side chain cleavage catalyzed by alliinase enzyme. The polypeptides are biocompatible as confirmed by cell viability assays and may find applications in drug delivery, biosensing and nanoreactor.