Secondary
Amine Pendant β‑Peptide Polymers
Displaying Potent Antibacterial Activity and Promising Therapeutic
Potential in Treating MRSA-Induced Wound Infections and Keratitis
posted on 2022-01-10, 21:03authored byYuxin Qian, Shuai Deng, Zihao Cong, Haodong Zhang, Ziyi Lu, Ning Shao, Sonia Abid Bhatti, Cong Zhou, Jiagao Cheng, Samuel H. Gellman, Runhui Liu
Interest in developing antibacterial
polymers as synthetic mimics
of host defense peptides (HPDs) has accelerated in recent years to
combat antibiotic-resistant bacterial infections. Positively charged
moieties are critical in defining the antibacterial activity and eukaryotic
toxicity of HDP mimics. Most examples have utilized primary amines
or guanidines as the source of positively charged moieties, inspired
by the lysine and arginine residues in HDPs. Here, we explore the
impact of amine group variation (primary, secondary, or tertiary amine)
on the antibacterial performance of HDP-mimicking β-peptide
polymers. Our studies show that a secondary ammonium is superior to
either a primary ammonium or a tertiary ammonium as the cationic moiety
in antibacterial β-peptide polymers. The optimal polymer, a
homopolymer bearing secondary amino groups, displays potent antibacterial
activity and the highest selectivity (low hemolysis and cytotoxicity).
The optimal polymer displays potent activity against antibiotic-resistant
bacteria and high therapeutic efficacy in treating MRSA-induced wound
infections and keratitis as well as low acute dermal toxicity and
low corneal epithelial cytotoxicity. This work suggests that secondary
amines may be broadly useful in the design of antibacterial polymers.