Peptide polymers which have excellent biocompatibility, bioactivity and biodegradability are an important class of biomedical materials with a wide range of biological functions and applications. Ring-opening polymerization of <i>N</i>-carboxyanhydrides (NCAs) has developed into a classical method for the preparation of peptide polymers, among which primary amines have been the most common initiators. However, the reaction rate of NCA polymerization initiated by primary amines is slow (usually need 2-3 days) and the reaction is moisture sensitivity. First, we developed new methods for the preparation of peptide polymers by fast and moisture-insensitive NCA ring-opening polymerization initiated by alkali-metal hexamethyldisilazide (Li/Na/KHMDS) or tetraalkylammonium carboxylate, which is more than 700 times faster than primary amine does. In particular, the new methods removed the limitations to the dependence on strict anhydrous solvent and glove box equipment. Second, by mimicking the key structural characteristic of host defense peptides (HDPs), we designed and discovered broad-spectrum antimicrobial peptide polymers. The optimal peptide polymers not only have stable and efficient antibacterial activity, killing 99.99% of bacteria within 1 hour, but also does not induce bacteria to develop resistance even after continuous use of the peptide polymer over 200 generations. Notably, the peptide polymer also effectively killed MRSA persister cells; in sharp contrast, vancomycin is inactive against MRSA persister cells. In addition, peptide polymers have shown in vivo therapeutic efficacy in a rabbit chronic osteomyelitis model caused by drug-resistant bacteria.

Study on rapid synthesis and antimicrobial function of peptide polymers

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