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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Cell Selectivity of an Antimicrobial Peptide Melittin Diastereomer with D-amino Acid in the Leucine Zipper Sequence

  • Zhu, Wan Long (Department of Bio-Materials, Graduate School, Chosun University) ;
  • Nan, Yong Hai (Research Center for Proteineous Materials and Department of Cellular & Molecular Medicine, School of Medicine, Chosun University) ;
  • Hahm, Kyung-Soo (Department of Bio-Materials, Graduate School, Chosun University) ;
  • Shin, Song-Yub (Department of Bio-Materials, Graduate School, Chosun University)
  • Published : 2007.11.30
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Abstract

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 $\alpha$-helical content in $\alpha$-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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References

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