Activity Based Profiling to Identify Active Proteases in Osteoarthritis
Abstract
Osteoarthritis (OA) is the most common form of arthritis in the world and develops in the joints resulting in inflammation. A defining characteristic of OA is the gradual destruction of cartilage coupled with an increase in proteolytic enzyme activity. The activation proteinase activated receptors (PARs), a type of G-protein coupled receptors (GPCRs), has been found to increase joint inflammation in OA. Due to the irreversible action of proteolysis, proteolytic activity is highly regulated within cellular systems. The expression of matrix metalloproteases (MMPs) and serine proteases have been identified in OA. We present a novel activity-based probe (ABP) that covalently binds to MMPs in OA synovial fluid. A previously reported serine ABP was also synthesized and was found to target trypsin-like serine proteases in OA synovial fluid. These probes are useful chemical tools that can identify active proteases in OA.