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  • Title: A new role for old ligands: discerning chelators for zinc metalloproteinases.
    Author: Jacobsen FE, Lewis JA, Cohen SM.
    Journal: J Am Chem Soc; 2006 Mar 15; 128(10):3156-7. PubMed ID: 16522091.
    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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