Solution structure of a designed amphipathic antimicrobial synthetic peptide, PGAa.
A designed peptide, PGAa showed an excellent antifungal activity as well as an efficient bactericidal activity toward gram-positive, especially in the pathogenic yeast Candida albicans 28838. The solution structures of PGAa have been determined both in 40% TFE/water solution and DPC micelle by CD and NMR spectroscopy. Based on NOEs, vicinal coupling constants, backbone amide exchange rates, and chemical shift indices, PGAa formed a long amphipathic alpha-helical conformation in both TFE and DPC micelle environments, spanning the residues Ile(2)-Ala(19) in TFE and Lys(5)-Ala(19) in DPC micelle, respectively. Solution structures suggested that the hydrophobic residues would interact with the fatty acyl chains of the lipid bilayer, while the positively charged side-chains exposed to aqueous environments. Therefore, we conclude that the alpha-helical structure as well as the highly amphiphatic nature of PGAa peptide may play a critical role in its antimicrobial activity as well as selectivities in different species.
Hong
E
E
Department of Biochemistry, Yonsei University, Seoul, 120-749, Korea.
Jeong
P Y
PY
Jung
J W
JW
Kim
Y
Y
Cheong
C
C
Paik
Y K
YK
Lee
W
W
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism; D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides; D002175:Candida / Q000187:drug effects* / Q000254:growth & development; D002942:Circular Dichroism; D006860:Hydrogen Bonding; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008823:Micelles; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D012996:Solutions; D013045:Species Specificity; D013329:Structure-Activity Relationship; D014269:Trifluoroacetic Acid / Q000378:metabolism; D014867:Water / Q000378:metabolism
D000890:Anti-Infective Agents; D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D008823:Micelles; D010455:Peptides; D012996:Solutions; C415869:antimicrobial peptide, PGAa; D014867:Water; D015060:1,2-Dipalmitoylphosphatidylcholine; D014269:Trifluoroacetic Acid