New chemosynthetic route to linear ε-poly-lysine

Abstract

ε-Poly-lysine (ε-PL) is an uncommon cationic, naturally-occurring homopolymer produced by the fermentation process. Due to its significant antimicrobial activity and nontoxicity to humans, ε-PL is now industrially produced as an additive, <i>e.g.</i> for food and cosmetics. However, the biosynthetic route can only make polymers with a molecular weight of about 3 kDa. Here, we report a new chemical strategy based on ring-opening polymerization (ROP) to obtain ε-PL from lysine. The 2,5-dimethylpyrrole protected α-amino-ε-caprolactam monomer was prepared through cyclization of lysine followed by protection. ROP of this monomer, followed by the removal of the protecting group, 2,5-dimethylpyrrole, ultimately yielded ε-PL with varying molecular weights. The structure of this chemosynthetic ε-PL has been fully characterized by ¹H NMR, ¹³C NMR, and MALDI-TOF MS analyses. This chemosynthetic ε-PL exhibited a similar p<i>K</i>_a value and low cytotoxicity as the biosynthetic analogue. Using this new chemical strategy involving ROP without the need for phosgene may enable a more cost effective production of ε-PL on a larger-scale, facilitating the design of more advanced biomaterials.