Abstract
Researchers in the post-genome era are confronted with the daunting task of assigning structure and function to tens of thousands of encoded proteins. To realize this goal, new technologies are emerging for the analysis of protein function on a global scale, such as activity-based protein profiling (ABPP), which aims to develop active site-directed chemical probes for enzyme analysis in whole proteomes. For the pursuit of such chemical proteomic technologies, it is helpful to derive inspiration from protein-reactive natural products. Natural products use a remarkably diverse set of mechanisms to covalently modify enzymes from distinct mechanistic classes, thus providing a wellspring of chemical concepts that can be exploited for the design of active-site-directed proteomic probes. Herein, we highlight several examples of protein-reactive natural products and illustrate how their mechanisms of action have influenced and continue to shape the progression of chemical proteomic technologies like ABPP.
Original language | English (US) |
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Pages (from-to) | 5788-5809 |
Number of pages | 22 |
Journal | Angewandte Chemie - International Edition |
Volume | 44 |
Issue number | 36 |
DOIs | |
State | Published - Sep 4 2005 |
All Science Journal Classification (ASJC) codes
- General Chemistry
- Catalysis
Keywords
- Enzymes
- Inhibitors
- Molecular probes
- Natural products
- Structure-activity relationships