Document Detail

Acyl-substituted dermaseptin S4 derivatives with improved bactericidal properties, including on oral microflora.
MedLine Citation:
PMID:  17043126     Owner:  NLM     Status:  MEDLINE    
The 15-mer dermaseptin S4 derivative S4(1-15) was recently shown to exhibit potent activity against oral pathogens associated with caries and periodontitis. Here, we investigated possible modes for improving the peptide's properties through systematic replacement of an N-terminal amino acid(s) with various fatty acids that modulate the peptide's hydrophobicity and/or charge. Deletion of 1 to 3 residues led to progressive loss of potency as assessed by MIC experiments performed on four test bacteria. Replacing the deleted amino acids with fatty acids most often resulted in potency recovery or improvement, as evidenced by lower MICs and faster bactericidal kinetics in culture media. Best results were obtained after replacement of the N-terminal dipeptide alanine-leucine with heptanoic (C7) or aminododecanoic (NC12) acid. Circular dichroism analysis correlated antibacterial properties to the peptide's secondary structure. MIC experiments and confocal laser scanning microscopy results indicated that C7-S4(3-15) and NC12-S4(3-15) were bactericidal to various oral pathogens, including those which are immobilized in a biofilm. C7-S4(3-15) performed similarly to or better than (depending on growth medium) IB-367, a peptide assessed in clinical trials for treatment of oral mucositis, reducing CFU counts by >3 log units within 2 min of incubation. Collectively, the data indicate that substitution of fatty acids for amino acids may be a useful strategy in revealing improved derivatives of known antimicrobial peptides and suggest the suitability of such compounds for controlling pathogens associated with oral diseases.
Y Porat; K Marynka; A Tam; D Steinberg; A Mor
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-10-16
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  50     ISSN:  0066-4804     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-11-23     Completed Date:  2007-01-04     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4153-60     Citation Subset:  IM    
Department of Biotechnology & Food Engineering, Technion-Israel Institute of Technology, Haifa, Israel.
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MeSH Terms
Amino Acid Sequence
Amino Acid Substitution
Amphibian Proteins / chemical synthesis,  chemistry*,  pharmacology*
Anti-Bacterial Agents / chemistry*,  pharmacology*
Antimicrobial Cationic Peptides / chemical synthesis,  chemistry*,  pharmacology*
Biofilms / drug effects
Circular Dichroism
Colony Count, Microbial
Fatty Acids / chemistry
Microbial Sensitivity Tests
Microscopy, Confocal
Mouth / drug effects*,  microbiology
Peptides / pharmacology
Protein Structure, Secondary
Structure-Activity Relationship
Reg. No./Substance:
0/Amphibian Proteins; 0/Anti-Bacterial Agents; 0/Antimicrobial Cationic Peptides; 0/Fatty Acids; 0/Peptides; 0/antimicrobial peptide IB-367; 136212-91-4/dermaseptin

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