Novel Stapling by Lysine Tethering Provides Stable and Low Hemolytic Cationic Antimicrobial Peptides
journal contributionposted on 08.04.2020, 17:34 by Hong Li, Yuchen Hu, Qi Pu, Tong He, Qianyu Zhang, Wen Wu, Xuefeng Xia, Jinqiang Zhang
Cationic 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