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XMP.629, a Peptide Derived from Functional Domain II of BPI, Demonstrates Broad-Spectrum Antimicrobial and Endotoxin-Neutralizing Properties In Vitro and In Vivo.

LIM E, AMMONS S, MOHLER V, KILLIAN D, MALLADI A, GIKONYO K, LIN J; Interscience Conference on Antimicrobial Agents and Chemotherapy (41st : 2001 : Chicago, Ill.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2001 Dec 16-19; 41: abstract no. F-346.

XOMA (US) LLC, Berkeley, CA

BACKGROUND: Bactericidal/permeability-increasing protein (BPI) and compounds derived from it have anti-infective and anti-angiogenic properties. We have used directed synthesis to design a low molecular weight peptidomimetic (XMP.629) derived from functional domain II of human BPI and have investigated its anti-infective properties in vitro and in vivo. METHODS: In vitro antibacterial activity was determined using the NCCLS broth dilution protocol followed by plating on nutrient agar to confirm microbicidal action. Antifungal testing was performed in Sabourauds dextrose broth. Endotoxin-neutralizing activity was assessed using the RAW 264.7 cell differentiation assay. In vivo studies were performed on CD-1 mice in acute peritonitis and acute endotoxemia models. Mice were challenged IP with 1.4x10[7] CFU/mL E. coli O7:K1 and treated IP with XMP.629 or saline. In the endotoxemia model, mice were challenged IV with 25 mg/kg E. coli O111:B4 lipopolysaccharide and treated IV with XMP.629 or saline. In both models, mortality was recorded for seven days. RESULTS: XMP.629 exhibited microbicidal activity on clinically relevant organisms including Staphylococcus aureus, Pseudomonas aeruginosa,and Candida albicans. In acute peritonitis, XMP.629 treatment resulted in a dose dependent, significant increase in survival when compared to saline: 1 mg/kg (6 survivors/15 total, P<0.05), 3 mg/kg (11/15, P<0.001), 10 mg/kg (12/15, P<0.001) and saline (1/15). In acute endotoxemia, XMP.629 treatment resulted in a significant increase in survival when compared to saline: 1 mg/kg (14/15, P<0.01), 3 mg/kg (15/15, P<0.005), 10 mg/kg (14/15, P<0.01) and saline (5/15). CONCLUSION: XMP.629 demonstrated broad spectrum microbicidal and endotoxin-neutralizing activity, and represents a novel anti-infective agent.

Publication Types:
  • Meeting Abstracts
  • Animals
  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Blood Proteins
  • Endotoxemia
  • Endotoxins
  • Humans
  • In Vitro
  • Lipopolysaccharides
  • Membrane Proteins
  • Mice
  • Peptides
  • Peritonitis
  • Pseudomonas aeruginosa
  • Ribonucleotides
  • bactericidal permeability increasing protein
  • immunology
  • xanthosine monophosphate
Other ID:
  • GWAIDS0030254
UI: 102269891

From Meeting Abstracts

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