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Design of novel analogue peptides with potent fungicidal but low hemolytic activity based on the cecropin a‐melittin hybrid structure
Author(s) -
Lee Dong Gun,
Park JungHyun,
Shin Song Yub,
Lee Sung Gu,
Lee Myung Kyu,
Kim Kil Lyong,
Hahm KyungSoo
Publication year - 1997
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/15216549700204281
Subject(s) - melittin , peptide , propidium iodide , biochemistry , chemistry , biology , microbiology and biotechnology , apoptosis , programmed cell death
In order to design synthetic peptides with potent antifungal activity but low cytotoxic activity under physiological conditions, several analogues of the previously reported cecropin A (CA)‐melittin (ME) hybrid peptide, CA(1‐8)‐ME(1‐12), were synthesized. These analogues were designed by analysis of the α‐helical wheel diagram of CA(1‐8)‐ME(1‐12). Antifungal activities were measured by growth inhibition of the yeast Trichosporon beigelii and by hemolytic assay with human red blood cells, respectively. Substitution of Thr for Lys at position 18 and 19 of CA(1‐8)‐ME(1‐12) caused a dramatic reduction in hemolytic activity. Two analogue peptides (analogue I and III) showed more potent antifungal and lower hemolytic activity than the original peptide. To study the antifungal mechanism of these peptides, fluorescence activated flow cytometry and confocal laser scanning microscopy were performed with the most powerful antifungal analogue I peptide designed in the present study. As determined by propidium iodide staining, fungal cells treated with analogue I or melittin showed higher fluorescence intensity than those treated with the weak antifungal peptide, cecropin A. By confocal microscopy the analogue I was detected in the intracellular region as well as the in cell membrane. These facts suggested that the antifungal function of this novel peptide analogue acts by pore formation in the cell membrane.