To bind zinc or not to bind zinc: An examination of innovative approaches to improved metalloproteinase inhibition

This short review highlights some recent advances in matrix metalloproteinase inhibitor (MMPi) design and development. Three distinct approaches to improved MMP inhibition are discussed: (1) the identification and investigation of novel zinc-binding groups (ZBGs), (2) the study of non-zinc-binding M...

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Bibliographic Details
Published in:Biochimica et biophysica acta 2010, Vol.1803 (1), p.72-94
Main Authors: Jacobsen, Jennifer A., Major Jourden, Jody L., Miller, Melissa T., Cohen, Seth M.
Format: Article
Language:English
Subjects:
Animals
Drug Design
Humans
Mechanism-based inhibitor
Metalloproteases - antagonists & inhibitors
Metalloproteases - chemistry
Metalloproteases - classification
MMP
Models, Molecular
Protease Inhibitors - chemistry
Protease Inhibitors - pharmacology
Substrate Specificity - drug effects
Zinc - metabolism
Zinc-binding group
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Summary:This short review highlights some recent advances in matrix metalloproteinase inhibitor (MMPi) design and development. Three distinct approaches to improved MMP inhibition are discussed: (1) the identification and investigation of novel zinc-binding groups (ZBGs), (2) the study of non-zinc-binding MMPi, and (3) mechanism-based MMPi that form covalent adducts with the protein. Each of these strategies is discussed and their respective advantages and remaining challenges are highlighted. The studies discussed here bode well for the development of ever more selective, potent, and well-tolerated MMPi for treating several important disease pathologies.
ISSN:0167-4889
0006-3002
1879-2596
DOI:10.1016/j.bbamcr.2009.08.006