Scale-up Efficient Synthesis of α-Poly(L-lysine)

α-Poly(_(L)-lysine)(α-PLL)is a water-soluble cationic biopolymer containing the monomeric unitα-_(L)-lysine,which not only possesses excellent intrinsic properties but also can be modified via facile reactions between the side amine groups and many other functional moieties.Ring-opening polymerization(ROP)is the most prevalently used technique for the synthesis of PL_(L)-based polypeptides,which involves initial conversion of theε-primary amine-protectedα-_(L)-lysine to the _(L)-lysine NCA monomer.However,obtaining N-carboxyanhydrides(NCAs)in high purity has been a formidable challenge for over 50 years,let alone the large-scale synthesis.Herein,we show an unprecedented scale-up synthesis of _(L)-Cbz-LysNCA monomer and its polymers,generating linearα-poly(_(L)-lysine)with molecular weight(MW)up to 13.4 kDa.This easy operated scale-up strategy will lay the foundations for the industrial preparation of _(L)-Cbz-LysNCA and its polymers,and further extend the realm of existing applications,offering a paradigm for scale-up synthesis of other polypeptides.