Antibacterial peptides interacting with model membranes. Spectroscopic study

L. Bednárová¹, M. Pazderková^1,2, P. Maloň¹, H. Dlouhá¹, E. Kočišová² and V. Kopecký²

¹Institute of Organic Chemistry and Biochemistry, Flemingovo n. 2, Prague 6, 166 10, Czech Republic ²Charles University in Prague, Institute of Physics, Ke Karlovu 5, Praha 2, 121 165, Czech Republic

bednarova@uochb.cas.cz

Naturally occurring antimicrobial peptides (AMPs) represent one successful form of chemical defense of eukaryotic cells against bacteria, protozoa, fungi, and viruses [1]. Many of them have been already isolated, thousands of their synthetic analogs were synthesized and a broad spectrum of their antimicrobial, anticancer and antiviral activities was proven [2,3]. Despite large number of known AMPs and their therapeutic potency, exact mechanism of action remains a matter of controversy. There is a consensus that these peptides selectively disrupt cell membranes and it is believed that their amphiphatic structure plays an important role in this process.

Novel antibacterial peptide halictine 1 (Hal-1) from the venom of the eusocial bee Halictus sexcinctus was recently described and some of its analogs was synthetized [4]. For our purpose we selected some of analogs with already known biological activities to study influence of specific modifications of amino acid sequences on their behavior in the presence of membrane mimicking environment. Thus, we studied the influence of increasing amphipathicity, Arg/Lys exchange or of restricting the ability to form a-helical structure. Using various spectroscopic techniques including circular dichroism (CD), infrared(IR) and fluorescence spectroscopy we studied structural changes of chosen peptides induced by 2,2,2-trifluoroethanol (TFE) as a helix promoter, sodium dodecyl sulphate (SDS) as a very simple membrane model as well as interaction with more appropriate models represented by phospholipid bilayers mimicking mammalian and bacterial membranes in order to clarify differences in their biological activities and to suggest the mechanism of the action.

Grant Agency of the Czech Republic (208/10/0376) is gratefully acknowledged.

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L. Bednárová, J. Straka,V. Čeřovský, Amino Acids 3 (2010) 763–775