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

Мова статті: 
Англійська
Автор(и) статті: 
Kathi Scheinpflug, Heike Nikolenko, Igor V. Komarov, Marina Rautenbach, Margitta Dathe
Вихідні данні статті: 
Pharmaceuticals (Basel). Sep 2013; 6(9): 1130–1144.
Назва журналу: 
Pharmaceuticals
Рік публікації: 
2013
Volume: 
6
Issue: 
9
Ключові слова: 
cyclic hexapeptides, antimicrobial activity, mode of action, permeabilisation, chemical modification
Ключове слово: 
cyclic hexapeptides
Ключове слово: 
antimicrobial activity
Ключове слово: 
mode of action
Ключове слово: 
permeabilisation
Ключове слово: 
chemical modification
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.
Назва підрозділу: 
Кафедра супрамолекулярної хімії та біохімії
ІНСТИТУТ ВИСОКИХ ТЕХНОЛОГІЙ Матеріали дозволено використовувати на умовах GNU FDL без незмінюваних секцій та Creative Commons Attribution/Share-Alike
Дизайн: Інститут високих технологій
Ivan Ivanov