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KMID : 0380220070400061090
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Journal of Biochemistry and Molecular Biology
2007 Volume.40 No. 6 p.1090 ~ p.1094
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Cell Selectivity of an Antimicrobial Peptide Melittin Diastereomer with D-amino Acid in the Leucine Zipper Sequence
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Zhu Wan Long
Nan Yong Hai
Hahm Kyung-Soo
Shin Song-Yub
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Abstract
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Melittin (ME), a linear 26-residue non-cell-selective antimicrobial peptide, displays strong lytic activity against bacterial and human red blood cells. To design ME analogue with improved cell selectivity, we synthesized a melittin diastereomer (ME-D) with D-amino acid in the leucine zipper sequence (Leu-6, Lue-13 and Ile-20). Compared to ME, ME-D exhibited the same or 2-fold higher antibacterial activity but 8-fold less hemolytic activity. Circular dichroism analysis revealed that ME-D has much less &agr;-helical content in α-helical content in the presence of zwitterionic EYPC/cholesterol (10 : 1, w/w) liposomes compared to negatively charged EYPE/EYPG (7 : 3, w/w) liposomes. The blue shift of the fluorescence emission maximum of ME-D in zwitterionic EYPC/ cholesterol (10 : 1, w/w) liposomes was much smaller than in negatively charged EYPE/EYPG (7 : 3, w/w) liposomes. These results suggested that the improvement in therapeutic index/cell selectivity of ME-D is correlated with its less permeability to zwitterionic membranes.
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KEYWORD
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Antimicrobial peptide, Cell selectivity, Leucine zipper sequence, Melittin
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