Structure and antimicrobial properties of multivalent short peptides

Anne W. Young; Zhigang Liu; Chunhui Zhou; Filbert Totsingan; Nikhil Jiwrajka; Zhengshuang Shi; Neville R. Kallenbach

doi:10.1039/c0md00247j

Structure and antimicrobial properties of multivalent short peptides

Anne W. Young, Zhigang Liu, Chunhui Zhou, Filbert Totsingan, Nikhil Jiwrajka, Zhengshuang Shi, Neville R. Kallenbach

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

The emergence of multidrug-resistant (MDR) strains continues to threaten human health. Along with many efforts directed towards the development of antimicrobial peptides (AMPs) as potential antibiotics, we have designed and tested several series of multivalent AMPs in comparison with the natural AMP, indolicidin. Constructs include multivalent displays with different sequences, repeats and scaffolds, including dendrimers, brush-like structures and polymeric displays constructed by linking various peptides to polymaleic anhydride (PMA). A branched tetramer of dipeptides (RW)_4D demonstrates the highest level of effectiveness among the constructs of this study. The results also show that under extended exposure to sublethal doses of (RW)_4D and indolicidin over a 400 generations period, MDR strains elicit much lower levels of resistance than to traditional antibiotics or disinfectants such as ciprofloxacin, vancomycin, chlorhexidine and gentamicin.

Original language	English (US)
Pages (from-to)	308-314
Number of pages	7
Journal	MedChemComm
Volume	2
Issue number	4
DOIs	https://doi.org/10.1039/c0md00247j
State	Published - Apr 2011

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Pharmacology
Pharmaceutical Science
Drug Discovery
Organic Chemistry

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10.1039/c0md00247j

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abstract = "The emergence of multidrug-resistant (MDR) strains continues to threaten human health. Along with many efforts directed towards the development of antimicrobial peptides (AMPs) as potential antibiotics, we have designed and tested several series of multivalent AMPs in comparison with the natural AMP, indolicidin. Constructs include multivalent displays with different sequences, repeats and scaffolds, including dendrimers, brush-like structures and polymeric displays constructed by linking various peptides to polymaleic anhydride (PMA). A branched tetramer of dipeptides (RW)4D demonstrates the highest level of effectiveness among the constructs of this study. The results also show that under extended exposure to sublethal doses of (RW)4D and indolicidin over a 400 generations period, MDR strains elicit much lower levels of resistance than to traditional antibiotics or disinfectants such as ciprofloxacin, vancomycin, chlorhexidine and gentamicin.",

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AU - Young, Anne W.

AU - Liu, Zhigang

AU - Zhou, Chunhui

AU - Totsingan, Filbert

AU - Jiwrajka, Nikhil

AU - Shi, Zhengshuang

AU - Kallenbach, Neville R.

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AB - The emergence of multidrug-resistant (MDR) strains continues to threaten human health. Along with many efforts directed towards the development of antimicrobial peptides (AMPs) as potential antibiotics, we have designed and tested several series of multivalent AMPs in comparison with the natural AMP, indolicidin. Constructs include multivalent displays with different sequences, repeats and scaffolds, including dendrimers, brush-like structures and polymeric displays constructed by linking various peptides to polymaleic anhydride (PMA). A branched tetramer of dipeptides (RW)4D demonstrates the highest level of effectiveness among the constructs of this study. The results also show that under extended exposure to sublethal doses of (RW)4D and indolicidin over a 400 generations period, MDR strains elicit much lower levels of resistance than to traditional antibiotics or disinfectants such as ciprofloxacin, vancomycin, chlorhexidine and gentamicin.

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Structure and antimicrobial properties of multivalent short peptides

Abstract

ASJC Scopus subject areas

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