Development of novel, dual purpose, MOBSAM-based, specific inhibitors for MMP-2/9 to image and investigate their activity in inflammatory pathologies in vivo

Fluorescence reflectance Imaging (FRI) shows accumulation of Cy5-labelled MMP probe in a brain slice of an EAE mouse; immunofluorescence staining of the same brain slice for CD45+ leukocytes shows localization of leukocytes at sites of probe accumulation (arrows). Image to the right shows high magnification of the boxed area. Bars = 200μm.
© Lydia Sorokin, Günter Haufe

Principal investigators: Lydia Sorokin, Günter Haufe
Project time: 07/2013 - 06/2015
Project code: FF-2013-28

The project employs a novel strategy for the development of a gelatinase specific (MMP-2 and MMP-9) probe that can be used both as an inhibitor and as a tracer molecule. In contrast to current probes that target the Zn-containing active site, we are targeting the substrate-enzyme binding domain using MOBSAM as a lead structure. In vivo specificity is tested using the murine experimental autoimmune encephalomyelitis (EAE) model were previous work has defined precise stages and sites of gelatinase activity, and a pivotal role in disease induction. Combining the expertise of EAE and MMPs in the Sorokin lab with that of specific probe development in the Haufe lab, provides a unique opportunity to investigate whether specific detection of activated MMPs in neuroinflammation is feasible and if the imaging of activated MMPs represents a surrogate for clinical parameters.

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