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

E. LIM, S. AMMONS, V. MOHLER, D. KILLIAN, A. MALLADI, K. GIKONYO, J. LIN;

Author address: 

XOMA (US) LLC, Berkeley, CA.

Abstract: 

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 Sabouraud’s 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 1.4x107 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
2001

abstract No: 

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Full conference title: 

ICAAC 41st
    • ICAAC 41st