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Peptides
Volume 27, Issue 11, November 2006, Pages 2585-2591
 
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doi:10.1016/j.peptides.2006.05.022    
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Copyright © 2006 Elsevier Inc. All rights reserved.

Synthetic peptides derived from human antimicrobial peptide ubiquicidin accumulate at sites of infections and eradicate (multi-drug resistant) Staphylococcus aureus in mice

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Carlo P.J.M. Brouwera, Sylvia J.P. Bogaardsa, Marty Wulferinka, Markwin P. Veldersa and Mick M. Wellingb, Corresponding Author Contact Information, E-mail The Corresponding Author

aAM-Pharma, Bunnik, The Netherlands

bDepartment of Radiology, Section of Nuclear Medicine, Leiden University Medical Center (LUMC), C4-R Room 77, P.O. Box 9600, NL-2300 RC Leiden, The Netherlands


Received 28 March 2006; 
revised 22 May 2006; 
accepted 22 May 2006. 
Available online 11 July 2006.

Abstract

The presence and antimicrobial activity of antimicrobial peptides (AMPs) has been widely recognized as an evolutionary preserved part of the innate immune system. Based on evidence in animal models and humans, AMPs are now positioned as novel anti-infective agents. The current study aimed to evaluate the potential antimicrobial activity of ubiquicidin and small synthetic fragments thereof towards methicillin resistant Staphylococcus aureus (MRSA), as a high priority target for novel antibiotics. In vitro killing of MRSA by synthetic peptides derived from the α-helix or β-sheet domains of the human cationic peptide ubiquicidin (UBI 1–59), allowed selection of AMPs for possible treatment of MRSA infections. The strongest antibacterial activity was observed for the entire peptide UBI 1–59 and for synthetic fragments comprising amino acids 31–38. The availability, chemical synthesis opportunities, and size of these small peptides, combined with their strong antimicrobial activity towards MRSA make these compounds promising candidates for antimicrobial therapy and detection of infections in man.

Keywords: Antimicrobial peptide; Synthetic fragments; MRSA; In vitro killing; Experimental infections; Microbicidal activity; Technetium; Detection of infections

Article Outline

1. Introduction
2. Materials and methods
2.1. Peptides
2.2. Micro-organisms
2.3. In vitro killing assay
2.4. Animals
2.5. MRSA infections in mice
2.6. Targeting MRSA-infections in mice with technetium-99 m labeled UBI peptides
2.7. Statistical analysis
3. Results
3.1. Peptides
3.2. Antimicrobial efficacy in vitro
3.3. Antimicrobial efficacy in vivo
3.4. Targeting MRSA-infections in mice with technetium-99 m labeled UBI peptides
3.5. Correlations between UBI peptide characteristics and biological assays
4. Discussion
References



Corresponding Author Contact InformationCorresponding author. Tel.: +31 71 5261880; fax: +31 71 5266751.

Peptides
Volume 27, Issue 11, November 2006, Pages 2585-2591
 
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