Skip to content
2000
Volume 9, Issue 8
  • ISSN: 1386-2073
  • E-ISSN: 1875-5402

Abstract

Gelatinase B/MMP-9 fulfills crucial regulator or effector functions in disease states and may be pharmacologically targeted by specific inhibitors. The characteristics of cleavages of a natural gelatinase B substrate were simulated and amino acids with zinc-ion chelating side-groups were employed to design a library of peptide-based inhibitors. Here, we extend previous findings of combinatorial chemical synthesis and subsequent library deconvolution with a recently established high-throughput technology. This enabled us to study MMP inhibitors with two zinc-binding groups and to identify a new L-pyridylalanine-containing gelatinase B inhibitor. The peptide analog was found to inhibit, almost to the same degree, the neutrophil enzymes collagenase 2/ MMP-8 and MMP-9 and the monocytic tumor necrosis factor-β (TNF-β) converting enzyme (TACE/ADAM-17) in vitro and to protect mice against lethal endotoxinemia in vivo. These data illustrate the usefulness of the screening platform for protective inhibitor discovery and complement recent insights in the pathogenesis and treatment of shock syndromes.

Loading

Article metrics loading...

/content/journals/cchts/10.2174/138620706778249758
2006-09-01
2025-07-08
Loading full text...

Full text loading...

/content/journals/cchts/10.2174/138620706778249758
Loading

  • Article Type:
    Research Article
Keyword(s): endotoxin; inflammation; lipopolysaccharide; Matrix metalloproteinase; neutrophil; sepsis
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test