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Download fileNovel Stapling by Lysine Tethering Provides Stable and Low Hemolytic Cationic Antimicrobial Peptides
journal contribution
posted on 08.04.2020, 17:34 authored by Hong Li, Yuchen Hu, Qi Pu, Tong He, Qianyu Zhang, Wen Wu, Xuefeng Xia, Jinqiang ZhangCationic antimicrobial
peptides (CAMPs) are potent therapeutics
for drug-resistant bacterial infections. However, the clinical application
of CAMPs is hampered by its poor proteolytic stability and hemolytic
activity toward eukaryotic cells. Great efforts have been made to
design and generate derivatives of CAMPs with improved pharmacological
properties. Here, we report a novel stapling protocol, which tethers
two ε-amino groups of the lysine residue by the N-alkylation
reaction on the hydrophilic face of amphiphilic antimicrobial peptides.
A series of lysine-tethered stapled CAMPs were synthesized, employing
the antimicrobial peptide OH-CM6 as a model. Biological screening
of the stapled CAMPs provided an analogue with strong antimicrobial
activity, high proteolytic stability, and low hemolytic activity.
This novel stapling approach offers an important chemical tool for
developing CAMP-based antibiotics.
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chemical tooleukaryotic cellsBiological screeningstabilityNovel Staplinglysine residueamphiphilic antimicrobial peptidesLow Hemolytic Cationic Antimicrobial Peptides Cationic antimicrobial peptidesLysine Tethering Provides Stablenovel stapling approachantimicrobial activityCAMP-based antibioticsGreat effortsnovel stapling protocollysine-tethered stapled CAMPsstapled CAMPsN-alkylation reactionantimicrobial peptide OH-CM 6