Serine proteases are involved in many pathophysiological conditions throughout the human body (e.g. irritable bowel syndrome, acute lung injury, cancer, viral infections, …). As the lack of insight in the underlying mechanisms of these diseases hampers successful clinical development of new drugs, the main goal of this research topic is to develop, optimise and validate a set of tools to further unravel the role of proteases and support the development of protease inhibitors.
The activity of specific proteases can be measured using in-house protocols of serine protease assays. The lab of Medical Biochemistry has a lot of experience performing these experiments, but optimisation and validation of several assays is still necessary. The goal is to obtain highly selective fluorigenic serine protease assays that are low end and can be performed in all kinds of laboratories during (pre)clinical development of protease inhibitors. The assays can also be used in preclinical and clinical samples to determine the activity of a selected protease.
As the selectivity of the synthetic substrates generally used to measure protease activity is questioned, a more advanced profiling of the proteolytic activity in biological samples is still lacking. Determination of specific proteolytic profiles using synthetic peptides and mass spectrometry, can lead to new insights in pathophysiological processes and proteases can emerge as new drug targets. Moreover, specific peptide-cleavage patterns can be used to distinguish between closely related enzymes.