Structural studies of a peptide with immune modulating and direct antimicrobial activity.
The structure and function of the synthetic innate defense regulator peptide 1018 was investigated. This 12 residue synthetic peptide derived by substantial modification of the bovine cathelicidin bactenecin has enhanced innate immune regulatory and moderate direct antibacterial activities. The solution state NMR structure of 1018 in zwitterionic dodecyl phosphocholine (DPC) micelles indicated an α-helical conformation, while secondary structures, based on circular dichroism measurements, in anionic sodium dodecyl sulfate (SDS) and phospholipid vesicles (POPC/PG in a 1:1 molar ratio) and simulations revealed that 1018 can adopt a variety of folds, tailored to its different functions. The structural data are discussed in light of the ability of 1018 to potently induce chemokine responses, suppress the LPS-induced TNF-α response, and directly kill both Gram-positive and Gram-negative bacteria.
Wieczorek
Michal
M
Chemistry Department, University of British Columbia, Vancouver, BC, Canada.
Jenssen
Håvard
H
Kindrachuk
Jason
J
Scott
Walter R P
WR
Elliott
Melissa
M
Hilpert
Kai
K
Cheng
John T J
JT
Hancock
Robert E W
RE
Straus
Suzana K
SK
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology; D002417:Cattle; D002942:Circular Dichroism; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007155:Immunologic Factors / Q000737:chemistry* / Q000494:pharmacology; D008823:Micelles; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000737:chemistry; D017433:Protein Structure, Secondary; D021281:Quantitative Structure-Activity Relationship; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D007155:Immunologic Factors; D008823:Micelles; D010455:Peptides; D010456:Peptides, Cyclic; D014409:Tumor Necrosis Factor-alpha; C555052:innate defense regulating peptide 1018; D010767:Phosphorylcholine; C056454:bactenecin; D012967:Sodium Dodecyl Sulfate; C028810:dodecylphosphocholine