Role of acetylation and charge in antimicrobial peptides based on human beta-defensin-3.
Cationic antimicrobial peptides are an evolutionarily ancient and essential element of innate immunity in higher organisms. The precise mechanism by which these peptides exert their antimicrobial activity on bacteria is not well understood. Decapeptides based on the C-terminus of human beta-defensin-3 were designed and evaluated to study the role of charge in defining the antimicrobial activity and selectivity of these peptides against Escherichia coli. Acetylated derivatives of these peptides were prepared in order to further evaluate how positively charged primary amines contribute to potency in these small antimicrobial peptides. These peptides enabled us to explore the relationship between net charge, charge distribution and antimicrobial activity. While the results indicate that net charge is a major factor in antimicrobial activity in these peptides, the actual relationship between charge and potency appears to be more complex.
Papanastasiou
Emilios Andrew
EA
Department of Chemistry and Biochemistry, George Mason University, Fairfax, VA 22030, USA.
Hua
Quyen
Q
Sandouk
Aline
A
Son
U Hyon
UH
Christenson
Andrew James
AJ
Van Hoek
Monique Louise
ML
Bishop
Barney Michael
BM
D000107:Acetylation; D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004927:Escherichia coli Infections / Q000188:drug therapy; D048168:Escherichia coli K12 / Q000187:drug effects; D006461:Hemolysis / Q000502:physiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship; D023083:beta-Defensins / Q000737:chemistry*
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; C422950:DEFB103A protein, human; D023083:beta-Defensins