Improved Antibacterial Activity of the Marine Peptide N6 against Intracellular Salmonella Typhimurium by Conjugating with the Cell-Penetrating Peptide Tat11 via a Cleavable Linker

Journal of Medicinal Chemistry
2018.0

Abstract

The poor penetration ability of antimicrobial agents limits their use in the treatment of intracellular bacteria. In this study, the conjugate CNC (6) was generated by connecting the cell-penetrating peptide Tat11 (1) and marine peptide N6 (2) via a cathepsin-cleavable linker, and the C-terminal aminated N6 (7) and CNC (8) were first designed and synthesized to eliminate intracellular Salmonellae Typhimurium. The cellular uptake of 6 and stability of 7 were higher than those of 2, and conjugates 6, 8, and 7 had almost no hemolysis and cytotoxicity. The antibacterial activities of 6, 8, and 7 against S. Typhimurium in RAW264.7 cells were increased by 67.2-76.2%, 98.6-98.9%, and 96.3-97.6%, respectively. After treatment with 1-2 μmol/kg of 6, 8, or 7, the survival of the S. Typhimurium-infected mice was 66.7-100%, higher than that of 2 (33.4-66.7%). This result suggested that 6, 8, and 7 may be excellent candidates for novel antimicrobial agents to treat intracellular pathogens.

Knowledge Graph

Similar Paper

Improved Antibacterial Activity of the Marine Peptide N6 against Intracellular Salmonella Typhimurium by Conjugating with the Cell-Penetrating Peptide Tat<sub>11</sub> via a Cleavable Linker
Journal of Medicinal Chemistry 2018.0
Improved antibacterial activity of a marine peptide-N2 against intracellular Salmonella typhimurium by conjugating with cell-penetrating peptides-bLFcin6/Tat11
European Journal of Medicinal Chemistry 2018.0
Synthesis and antibacterial study of cell-penetrating peptide conjugated trifluoroacetyl and thioacetyl lysine modified peptides
European Journal of Medicinal Chemistry 2021.0
Simplified lipid II-binding antimicrobial peptides: Design, synthesis and antimicrobial activity of bioconjugates of nisin rings A and B with pore-forming peptides
Bioorganic &amp; Medicinal Chemistry 2018.0
Novel Cell-Penetrating Peptide Conjugated Proteasome Inhibitors: Anticancer and Antifungal Investigations
Journal of Medicinal Chemistry 2020.0
Design and synthesis of novel antibacterial peptide-resin conjugates
Bioorganic &amp; Medicinal Chemistry Letters 2007.0
In vitro biological evaluation of new antimycobacterial salicylanilide-tuftsin conjugates
European Journal of Medicinal Chemistry 2017.0
Antimicrobial activity and mode of action of novel, N-terminal tagged tetra-peptidomimetics
MedChemComm 2013.0
Lysine-Tethered Stable Bicyclic Cationic Antimicrobial Peptide Combats Bacterial Infection in Vivo
Journal of Medicinal Chemistry 2022.0
Antimicrobial Peptides with Potential for Biofilm Eradication: Synthesis and Structure Activity Relationship Studies of Battacin Peptides
Journal of Medicinal Chemistry 2015.0