B/PI-derived synthetic peptides: synergistic effects in tethered bactericidal and endotoxin neutralizing peptides

Beulah H. Gray, Judith R. Haseman, Kevin H Mayo

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Human neutrophil bactericidal protein (B/PI) is known for its ability to kill bacteria and to neutralize the action of endotoxin. Short lininear 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/Pl 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.

Original languageEnglish (US)
Pages (from-to)185-190
Number of pages6
JournalBBA - General Subjects
Volume1244
Issue number1
DOIs
StatePublished - May 11 1995

Bibliographical note

Funding Information:
This work was supported by Cystic Fibrosis Foundation Grant CFF/NIH RFA 5578 and, in part, by National Institutes of Health Grant Al 26159. We are grateful to Eric Eccleston and Denisha Walik of the Microchemical Facility for their patient cooperation during the synthesis of peptides. We thank Paul Fudally for technical assistance and Letitia Yao for performing the NMR conformational studies.

Keywords

  • Antibiotic
  • B/PI
  • Bactericidal protein
  • Endotoxin neutralization
  • Peptide

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