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Title 

Design of novel analogue peptides with potent fungicidal but low hemolytic activity based on the cecropin A-melittin hybrid structure

Authors 

Dong Gun LeeJung Hyun ParkSong Yub ShinSung Gu LeeMyung Kyu LeeKil Lyong KimKyung Soo Hahm

Publisher 

International Union of Biochemistry and Molecular Biology

Issue Date 

1997

Citation 

Biochemistry and Molecular Biology International, vol. 43, no. 3, pp. 489-498

Keywords 

antifungal activitycecropin Amelittinhemolytic activityhybrid peptideTrichosporon beigelii

Abstract 

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.

ISSN 

1039-9712

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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