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Design, synthesis and application of activity-based probes for imaging and detection of proteases

Therefore, it is not surprising that mis regulation of proteases can lead to a wide variety of diseases. Proteases are generally translated as inactive zymogens and need proteolytic processing to become active. To specifically label the active form of proteases, we develop and use activity-based probes (ABPs – Figure 1B). These are often derived from electrophilic inhibitors that react in a mechanism-based manner with the active site machinery. This reaction leads to covalent attachment of a detection tag, which can be used for visualization, analysis or enrichment of the active protease species.  In this project, you will be responsible for the synthesis of such probes using solution and solid phase organic synthesis techniques and/or the evaluation within a complex proteome or in cell culture.

  • The project is available in the Fall and Spring semester.
  • Number of places available: 1 per semester.

Prerequisites

  • Either experience with chemical synthesis or with biochemistry is required.

Faculty Department

Faculty of Biomedical Sciences / Cellular & Molecular Medicine Dept.

The department combines expertise in techniques of bio-organic chemistry, biochemistry, electrophysiology, molecular biology, cell imaging, proteomics, bio-informatics and animal model development to acquire new insights into cellular signaling and communication processes. An additional aim is to decipher the molecular basis for human signal-transduction related diseases and to identify novel therapeutic targets. The department consists of 14 research groups, maintaining close contacts with other departments of the KU Leuven and with the University Hospital. The laboratory of chemical biology specializes in the design and synthesis of chemical probes to  covalently label proteins of interests in cells and cell lysates.