Poly(ʟ-Cysteine) Based Functional Polypeptides

Abstract

Stimuli-responsive polymers are promising materials that aim to mimic the adaptive responses of biological systems like proteins, which respond to changes in pH, oxidation, and other stimuli. Polypeptides stand out because of biocompatibility, biodegradability and their inherent nature of adopting ordered secondary structures that allow them to respond to stimuli specific to conformation. tert-butylbenzene functionalized poly(ʟ-cysteine) based thioether polymers were synthesized via steric-hinderance assisted ring opening polymerization of N-carboxyanhydride monomer tailor-made via multi-step organic synthesis. The polymer was oxidized using various oxidants and the oxidation-responsive behaviours were investigated. The thioether functionality was oxidized to sulfoxide and sulfone groups in a controlled manner. These tert-butylbenzene functionalized poly(ʟ-cysteine) adopted predominantly α-helical conformation which was maintained even after oxidation. Also, increase in the hydrophilicity was observed after oxidization. Further, thiol functionalized soluble random and block copolymers were synthesized using tBuBnCys and CbzCys and were subjected to oxidation. The deprotected block copolymer which initially adopted mixed conformation with predominant β-sheet, adopted an α-helical conformation thus switching the conformation on oxidation. Also, the thiol functional handle was used for metal-free thiol-ene click reaction during post-polymerization. The polymers were characterized by NMR, SEC, CD, TGA, DSC etc. Real-time FTIR kinetics was also done to ensure living nature of the polymers. DLS studies were also done to monitor the sizes before and after oxidation.