Journal
JOURNAL OF PEPTIDE SCIENCE
Volume 15, Issue 9, Pages 589-594Publisher
WILEY
DOI: 10.1002/psc.1155
Keywords
antimicrobial activity; hemolysis; HPA3NT3-analog peptide; leakage of calcein; molecular dynamics
Funding
- National Research Foundation of Korea [핵06B1611, 2008-2000123, 핵06B3109] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
In this study, a HPA3NT3-analog (FKKLKKLFKKILKLK-NH2) peptide was designed. In this analog, two Trp residues (positions 12, 14) were replaced with Leu, and Arg and Asn (positions 3, 13) were replaced with Lys to investigate the role of amino acid substitution and increased cationicity on antimicrobial and hemolytic activities. In fungal and Gram-negative bacterial cells, HPA3NT3-analog activity was unchanged or slightly enhanced when compared to the HPA3NT3 peptide. In addition, a twofold decrease in activity against Gram-positive bacteria was observed. The HPA3NT3-analog also induced less hemolysis (4.2%) than the HPA3NT3 peptide (71%) at 200 mu m. Circular dichroism (CID) spectra revealed that the HPA3NT3-analog peptide had an unordered structure in buffer and egg yolk L-2-phosphatidyl choline (EYPC), but adapted an alpha-helical conformation in 50% 2,2,2-trifluoroethanol (TFE) and negatively charged egg yolk L-2-phosphatidyl glycerol (EYPG), while the parent peptide showed an ordered structure in the EYPC. Additionally, the HPA3NT3-analog peptide induced the leakage of calcein from egg yolk L-2-phosphatidyl ethanolamine (EYPE)/EYPG (7:3 w/w) large unilamellar vesicles (LUVs); however, the activity was slightly weaker than that of the HPA3NT3 peptide. The molecular dynamics (MD) structures revealed that the amino acid substitutions induced a significant variation in peptide structure. These results suggest that the substitutions of Arg and Asn with Lys and two Trp with Leu resulted in small changes in HPA3NT3-analog activity and significant decreases in hemolytic activity. Copyright (C) 2009 European Peptide Society and John Wiley & Sons, Ltd.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available