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

a-Poly((L)-lysine) (a-PLL) is a water-soluble cationic biopolymer containing the monomeric unit a-(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 PLL-based polypeptides, which involves initial conversion of the e-primary amine-protected a-(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 linear a-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.