Target identification of natural products and bioactive compounds using affinity-based probes

Area of Science:

• Chemical Biology
• Drug Discovery
• Proteomics

Background:

• Advances in natural product isolation and synthesis have increased the availability of bioactive compounds.
• A significant challenge remains in identifying the specific biological targets of these compounds.
• Understanding compound-target interactions is key to uncovering new therapeutic strategies.

Purpose of the Study:

• To highlight recent advances in identifying natural product and bioactive compound targets using affinity-based probes.
• To review the development and application of photoaffinity labeling techniques for target identification.
• To discuss the strengths, weaknesses, and future outlook of proteome-wide profiling strategies.

Main Methods:

• Utilizing affinity-based probes, including photoaffinity labeling, to capture compound-protein interactions.
• Employing photoactivatable groups that can be incorporated into bioactive compounds.
• Analyzing captured targets to identify direct and indirect interactions within live cells.

Main Results:

• Photoaffinity labeling allows for the direct capture of cellular targets of bioactive compounds in live cells.
• This method is effective even for compounds with reversible or moderate-affinity interactions.
• Identification of targets can reveal molecular pathways and potential therapeutic applications.

Conclusions:

• Affinity-based probes, especially photoaffinity labeling, are powerful tools for identifying bioactive compound targets.
• This approach facilitates the discovery of new therapeutic targets and pathways for diseases.
• Further development of photoactivatable groups will enhance proteome-wide profiling capabilities.