a.Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
b.University of Science and Technology of China, Hefei 230026, China
hanmiaomiao@ciac.ac.cn (M.M.H.)
sji@ciac.ac.cn (S.X.J.)
收稿:2022-07-18,
修回:2022-8-18,
录用:2022-8-23,
网络首发:2022-10-20,
纸质出版:2023-03-01
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Liu, H.; Liu, X.; Cao, Y. Q.; Liu, M.; Han, M. M.; Ji, S. X. Engineering antibacterial activities and biocompatibility of hyperbranched lysine-based random copolymers. Chinese J. Polym. Sci. 2023, 41, 345–355
Hui Liu, Xiao Liu, Yuan-Qiao Cao, et al. Engineering Antibacterial Activities and Biocompatibility of Hyperbranched Lysine-based Random Copolymers[J]. Chinese Journal of Polymer Science, 2023, 41(3): 345-355.
Liu, H.; Liu, X.; Cao, Y. Q.; Liu, M.; Han, M. M.; Ji, S. X. Engineering antibacterial activities and biocompatibility of hyperbranched lysine-based random copolymers. Chinese J. Polym. Sci. 2023, 41, 345–355 DOI: 10.1007/s10118-022-2859-1.
Hui Liu, Xiao Liu, Yuan-Qiao Cao, et al. Engineering Antibacterial Activities and Biocompatibility of Hyperbranched Lysine-based Random Copolymers[J]. Chinese Journal of Polymer Science, 2023, 41(3): 345-355. DOI: 10.1007/s10118-022-2859-1.
The toxicity of hyperbranched poly(lysine) (HPL) was engineered by copolymerizing lysine with hydrophobic amino acids such as alanine
tryptophan
or phenylalanine to obtain hyperbranched random copolymers. These copolymers have comparable antibacterial activities to HPL while their cytotoxicities and in vivo toxicities are lowered.
Antimicrobial peptides (AMPs) have been considered as an alternative to small molecule antibiotics since they are difficult to develop antimicrobial resistance. Hyperbranched polylysine (HPL)
an AMP mimics
has gained attention due to its broad-spectrum antibacterial activities
but it also suffers from high toxicity. Here we report a facile strategy to engineer the toxicity of HPL by copolymerizing lysine (K) with a hydrophobic amino acid
e.g.
alanine (A)
tryptophan (W) or phenylalanine (F)
to afford hyperbranched random copolymers. These copolymers have comparable antibacterial activities to HPL while their cytotoxicities and
in vivo
toxicities are lowered when the type and content of hydrophobic amino acid and the size of copolymers are optimized. The
G. mellonella
infection model demonstrates that the copolymers are effective against the
S. aureus
infection
in vivo
. The copolymers kill the bacteria through the disruption of cell membranes and the bacteria do not develop resistance to the copolymers.
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