Labeled and Label-Free Target Identifications of Natural Products

Target identification, employing chemical proteomics,
constitutes
a continuous challenging endeavor in the drug development of natural
products (NPs). Understanding their targets is crucial for deciphering
their mechanisms and developing potential probes or drugs. Identifications
fall into two main categories: labeled and label-free techniques.
Labeled methods use the molecules tagged with markers such as biotin
or fluorescent labels to easily detect interactions with target proteins.
Thorough structure–activity relationships are essential before
labeling to avoid changes in the biological activity or binding specificity.
In contrast, label-free technologies identify target proteins without
modifying natural products, relying on changes in the stability, thermal
properties, or precipitation in the presence or absence of these products.
Each approach has its advantages and disadvantages, offering a comprehensive
understanding of the mechanisms and therapeutic potential of the NPs.
Here, we summarize target identification techniques for natural molecules,
highlight case studies of notable NPs, and explore future applications
and directions.