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

Pharmaceuticals

Kathi Scheinpflug³  Heike Nikolenko³  Igor V. Komarov²  Marina Rautenbach¹ 

[1] Department of Biochemistry, University of Stellenbosch, Private Bag X1, Matieland 7602, South Africa; E-Mail:;Institute of High Technologies, Kiev National Taras Shevchenko University, 64 Vladimirskaya st., Kiev 01033, Ukraine; E-Mail:;Leibniz-Institut für Molekulare Pharmakologie, Robert-Roessle-Str. 10, Berlin 13125, Germany; E-Mails:

关键词: cyclic hexapeptides;    antimicrobial activity;    mode of action;    permeabilisation;    chemical modification;   

DOI  :  10.3390/ph6091130

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.