Title:Phosphonate Emerging Zinc Binding Group in Matrix Metalloproteinase Inhibitors
VOLUME: 16 ISSUE: 14
Author(s):Cristina Campestre, Mariangela Agamennone, Marilena Tauro and Paolo Tortorella
Affiliation:Dipartimento di Farmacia- Scienze del Farmaco, Università degli Studi “Aldo Moro” di Bari, via Orabona 4, 70126 Bari, Italy.
Keywords:Bisphosphonate, Inhibitors, Matrix metalloproteinases, Metalloenzymes, Phosphonic acid, Zinc binding group.
Abstract:Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases, capable to degrade
the extracellular matrix (ECM) in physiologic conditions. Because of their overexpression and pivotal
role in many pathological events, they have been proposed as a therapeutic and prognostic target for a
number of diseases. Selectivity among MMPs is essential for realizing the clinical potential of inhibitors.
The design of MMP inhibitors (MMPIs) has largely focused on development of various compounds
containing a zinc binding group (ZBG) in their structure, with hydroxamate being the most potent one. Due to the
high degree of homology in the catalytic domain of all the MMPs, the specificity and selectivity of first generation hydroxamate
MMPIs were minimal, with several off-target effects and binding to other metzincins. This review highlights
the role of phosphonate as ZBG in the design and development of new MMPIs.
