B/PI-derived synthetic peptides: synergistic effects in tethered bactericidal and endotoxin neutralizing peptides.
Human neutrophil bactericidal protein (B/PI) is known for its ability to kill bacteria and to neutralize the action of endotoxin. Short linear peptides derived from residues 80-109 have been synthesized and their bactericidal and endotoxin neutralizing activities have been assayed. A series of 'walk-through' decapeptides, overlapping 3 to 4 residues, indicates that endotoxin neutralizing and partial bactericidal activities can be localized within the N- and C-terminal portions, respectively, of the 80-109 sequence. Bactericidal activity toward Pseudomonas aeruginosa was localized in central peptides of the walk-through series and greatest in peptide 90-99. By using longer peptides, residues 86-104 and 82-108, both bactericidal and endotoxin neutralizing activities are significantly enhanced. Bactericidal activity of peptide 82-108 is now only 6-fold less than that of parent B/PI and 9-fold more potent than peptide 86-104. The 82-108 peptide was 7-fold more active at endotoxin neutralization than 86-104 but showed less enhanced activity, being approx. 470-times less active than B/PI. Cyclized 82-108 peptide retained bactericidal activity but did not improve in capacity to neutralize endotoxin.
Gray
B H
BH
Department of Biochemistry, University of Minnesota, Minneapolis 55455, USA.
Haseman
J R
JR
Mayo
K H
KH
D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides; D001770:Blood Bactericidal Activity; D001798:Blood Proteins / Q000008:administration & dosage / Q000737:chemistry*; D004357:Drug Synergism; D004731:Endotoxins / Q000037:antagonists & inhibitors; D008033:Limulus Test; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000008:administration & dosage; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013329:Structure-Activity Relationship
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D004731:Endotoxins; D010446:Peptide Fragments; C053368:cationic antimicrobial protein 57, human