Journal
CHEMISTRY-A EUROPEAN JOURNAL
Volume 21, Issue 9, Pages 3540-3545Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.201404650
Keywords
antimicrobials; DNA; peptides; polyamides; selectivity
Categories
Funding
- IISER Bhopal
- Council for Scientific and Industrial Research
- Department of Biotechonology
- Department of Science and Technology
- Department of Biotechonology through RGYI [BT/PR15143/GBD/27/334/2011]
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Naturally occurring antimicrobial peptides (AMPs) are powerful defence tools to tackle pathogenic microbes. However, limited natural production and high synthetic costs in addition to poor selectivity limit large-scale use of AMPs in clinical settings. Here, we present a series of synthetic AMPs (SAMPs) that exhibit highly selective and potent killing of Mycobacterium (minimum inhibitory concentration <20gmL(-1)) over E.coli or mammalian cells. These SAMPs are active against rapidly multiplying as well as growth saturated Mycobacterium cultures. These SAMPs are not membrane-lytic in nature, and are readily internalized by Mycobacterium and mammalian cells; whereas in E.coli, the lipopolysaccharide layer inhibits their cellular uptake, and hence, their antibacterial action. Upon internalization, these SAMPs interact with the unprotected genomic DNA of mycobacteria, and impede DNA-dependent processes, leading to bacterial cell death.
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