EXC 1003 FF-2013-28 - Development of novel, dual purpose, MOBSAM-based, specific inhibitors for MMP-2/9 to image and investigate their activity in inflammatory pathologies in vivo

Basic data for this project

Description

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.