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De novo Design and Synthesis of Potent Antimicrobial Peptide and Mode of Action


Paper Type 
Contributed Paper
Title 
De novo Design and Synthesis of Potent Antimicrobial Peptide and Mode of Action
Author 
Nualyai Yaraksa and Sakda Daduang
Email 
nualyai.y@ubru.ac.th
Abstract:

As therapeutic potential, antimicrobial peptides (AMPs) with simple amino acid composition

and short length can be effective candidates for clinical and commercial development. KL12, a 12-amino
acid residual alpha-helical peptide with six-positive charges and 50% hydrophobicity, was designed by
de novo design based on unique characteristics of naturally occurring AMPs, chemically synthesized by
F-moc method and evaluated antimicrobial efficacy using broth microdilution assay. The antimicrobial
experiments revealed that KL12 strongly inhibited the growth of human pathogenic bacteria. The analysis
of minimum inhibitory concentrations (MICs) against Staphylococcus aureus ATCC25923, Staphylococcus
saprophyticus ATCC15035, Staphylococcus aureus MRSA DMST20654, Salmonella typhi DMST22842 and
Escherichia coli ATCC25922 showed that the MICs of KL12 were 2 μg/ml to 64 μg/ml. The modes
of action of KL12 were investigated further on bacterial cell surface and membrane. Interaction
with Lipopolysaccharide (LPS) and lipotheicoic acid (LTA) revealed that KL12 was able to bind and
neutralize LPS and LTA. Fluorescence studies and electron microscopy analyzes indicated that KL12
killed bacterial cell by permeabilizing the cell membrane and damaging membrane integrity.
Start & End Page 
444 - 459
Received Date 
2020-03-11
Revised Date 
Accepted Date 
2020-12-23
Full Text 
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Keyword 
KL12, antimicrobial peptides, designed peptides, peptides synthesis, mode of action
Volume 
Vol.48 No.2 (March 2021)
DOI 
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