doi: 10.1021/ja057957s.
A new role for old ligands: discerning chelators for zinc metalloproteinases
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- PMID: 16522091
- DOI: 10.1021/ja057957s
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A new role for old ligands: discerning chelators for zinc metalloproteinases
J Am Chem Soc.
.
Abstract
In an effort to identify promising non-hydroxamate inhibitors of matrix metalloproteinases (MMPs) several new zinc-binding groups (ZBGs) based on pyridine-derived or aza-macrocycle chelators have been examined. Fluorescence-based enzyme assays have been used to determine the IC50 values for these ZBGs against MMP-1, MMP-3, and anthrax lethal factor (LF). Many of these ligands were found to be remarkably potent, with IC50 values as much as 185-fold lower than that found for acetohydroxamic acid. These ligands are proposed to be more selective "warheads" for the inhibition of metalloenzymes that contain Zn2+ versus other metal ions at their active site.
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