Pharmaceuticals 2013, 6(9), 1130-1144; doi:10.3390/ph6091130
Article

What Goes around Comes around-A Comparative Study of the Influence of Chemical Modifications on the Antimicrobial Properties of Small Cyclic Peptides

1 Leibniz-Institut für Molekulare Pharmakologie, Robert-Roessle-Str. 10, Berlin 13125, Germany 2 Institute of High Technologies, Kiev National Taras Shevchenko University, 64 Vladimirskaya st., Kiev 01033, Ukraine 3 Department of Biochemistry, University of Stellenbosch, Private Bag X1, Matieland 7602, South Africa
* Author to whom correspondence should be addressed.
Received: 30 July 2013; in revised form: 26 August 2013 / Accepted: 2 September 2013 / Published: 6 September 2013
(This article belongs to the Special Issue Antimicrobial Agents)
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Abstract: Tryptophan and arginine-rich cyclic hexapeptides of the type cyclo-RRRWFW combine high antibacterial activity with rapid cell killing kinetics, but show low toxicity in human cell lines. The peptides fulfil the structural requirements for membrane interaction such as high amphipathicity and cationic charge, but membrane permeabilisation, which is the most common mode of action of antimicrobial peptides (AMPs), could not be observed. Our current studies focus on elucidating a putative membrane translocation mechanism whereupon the peptides might interfere with intracellular processes. These investigations require particular analytical tools: fluorescent analogues and peptides bearing appropriate reactive groups were synthesized and characterized in order to be used in confocal laser scanning microscopy and HPLC analysis. We found that minimal changes in both the cationic and hydrophobic domain of the peptides in most cases led to significant reduction of antimicrobial activity and/or changes in the mode of action. However, we were able to identify two modified peptides which exhibited properties similar to those of the cyclic parent hexapeptide and are suitable for subsequent studies on membrane translocation and uptake into bacterial cells.
Keywords: cyclic hexapeptides; antimicrobial activity; mode of action; permeabilisation; chemical modification

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MDPI and ACS Style

Scheinpflug, K.; Nikolenko, H.; Komarov, I.V.; Rautenbach, M.; Dathe, M. What Goes around Comes around-A Comparative Study of the Influence of Chemical Modifications on the Antimicrobial Properties of Small Cyclic Peptides. Pharmaceuticals 2013, 6, 1130-1144.

AMA Style

Scheinpflug K, Nikolenko H, Komarov IV, Rautenbach M, Dathe M. What Goes around Comes around-A Comparative Study of the Influence of Chemical Modifications on the Antimicrobial Properties of Small Cyclic Peptides. Pharmaceuticals. 2013; 6(9):1130-1144.

Chicago/Turabian Style

Scheinpflug, Kathi; Nikolenko, Heike; Komarov, Igor V.; Rautenbach, Marina; Dathe, Margitta. 2013. "What Goes around Comes around-A Comparative Study of the Influence of Chemical Modifications on the Antimicrobial Properties of Small Cyclic Peptides." Pharmaceuticals 6, no. 9: 1130-1144.

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