Matrix Metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that play a crucial role in the cleavage of extracellular proteins. Overexpression of MMPs has been associated with a number of pathologies such as arthritis and cancer. The activity of these metalloproteins can be controlled with inhibitors that coordinate to the catalytic metal. To obtain an inhibitor that is highly specific, a pro-drug approach has emerged as a way to control metal binding. This work explores the development of  inactive MMP pro-inhibitors (proMMPi) that can become activated, releasing a zinc binding group (ZBG), after deprotection by a specific stimulus, esterase. This project will also explore the responsiveness of protected zinc binding groups (pro-ZBGs) to esterase, and the kinetic efficiency of the release.

Activation of matrix metalloprotenaise proinhibitors by esterase

243rd National Meeting (2012)

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