Journal
CHEMBIOCHEM
Volume 15, Issue 15, Pages 2275-2280Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201402264
Keywords
antimicrobial peptides; Gram-negative bacteria; Gram-positive bacteria; hemolysis; resistance; solid-phase synthesis
Funding
- Elsa U. Pardee foundation
- National Science Foundation (NSF) [1351265]
- NSF [0964819]
- National Institutes of Health [GM101279]
- Direct For Mathematical & Physical Scien
- Division Of Chemistry [1351265] Funding Source: National Science Foundation
- Direct For Mathematical & Physical Scien
- Division Of Physics [0964819] Funding Source: National Science Foundation
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The last two decades have seen the rise of antimicrobial peptides (AMPs) to combat emerging antibiotic resistance. Herein we report the solid-phase synthesis of short lipidated /-AA hybrid peptides. This family of lipo-chimeric peptidomimetics displays potent and broad-spectrum antimicrobial activity against a range of multi-drug resistant Gram-positive and Gram-negative bacteria. These lipo-/-AA hybrid peptides also demonstrate high biological specificity, with no hemolytic activity towards red blood cells. Fluorescence microscopy suggests that these lipo-/-AA chimeric peptides can mimic the mode of action of AMPs and kill bacterial pathogens via membrane disintegration. As the composition of these chimeric peptides is simple, therapeutic development could be economically feasible and amenable for a variety of antimicrobial applications.
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