Effects of net charge and the number of positively charged residues on the biological activity of amphipathic α-helical cationic antimicrobial peptides

In our previous study, we utilized a 26‐residue amphipathic α‐helical antimicrobial peptide L‐V13K (Chen et al., Antimicrob Agents Chemother 2007, 51, 1398–1406) as the framework to study the effects of peptide hydrophobicity on the mechanism of its antimicrobial action. In this study, we explored t...

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Bibliographic Details
Published in:Biopolymers 2008, Vol.90 (3), p.369-383
Main Authors: Jiang, Ziqing, Vasil, Adriana I., Hale, John D., Hancock, Robert E. W., Vasil, Michael L., Hodges, Robert S.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
amphipathicity
Anti-Infective Agents - chemical synthesis
Anti-Infective Agents - chemistry
Anti-Infective Agents - isolation & purification
Anti-Infective Agents - metabolism
Anti-Infective Agents - pharmacology
antimicrobial activity
Antimicrobial Cationic Peptides - chemical synthesis
Antimicrobial Cationic Peptides - chemistry
Antimicrobial Cationic Peptides - isolation & purification
Antimicrobial Cationic Peptides - metabolism
Antimicrobial Cationic Peptides - pharmacology
antimicrobial peptide
Chromatography, High Pressure Liquid
Circular Dichroism
helicity
Hemolysis - drug effects
hemolytic activity
Humans
Hydrophobic and Hydrophilic Interactions
hydrophobicity
Microbial Sensitivity Tests
Molecular Sequence Data
peptide self-association
Protein Structure, Secondary
Pseudomonas aeruginosa - drug effects
Pseudomonas aeruginosa - genetics
Temperature
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Summary:In our previous study, we utilized a 26‐residue amphipathic α‐helical antimicrobial peptide L‐V13K (Chen et al., Antimicrob Agents Chemother 2007, 51, 1398–1406) as the framework to study the effects of peptide hydrophobicity on the mechanism of its antimicrobial action. In this study, we explored the effects of net charge and the number of positively charged residues on the hydrophilic/polar face of L‐V13K on its biological activity (antimicrobial and hemolytic) and biophysical properties (hydrophobicity, amphipathicity, helicity, and peptide self‐association). The net charge of V13K analogs at pH 7 varied between −5 and +10 and the number of positively charged residues varied from 1 to 10. The minimal inhibitory concentrations (MIC) against six strains of Pseudomonas aeruginosa as well as other gram‐negative and gram‐positive bacteria were determined along with the maximal peptide concentration that produces no hemolysis of human red blood cells (MHC). Our results show that the number of positively charged residues on the polar face and net charge are both important for both antimicrobial activity and hemolytic activity. The most dramatic observation is the sharp transition of hemolytic activity on increasing one positive charge on the polar face of V13K i.e., the change from +8 to +9 resulted in greater than 32‐fold increase in hemolytic activity (250 μg/ml to
ISSN:0006-3525
1097-0282
DOI:10.1002/bip.20911