Ligand Fishing: An Approach for the Discovery of Inhibitors from Complex Biological Mixtures

Recent advances on discovery of enzyme inhibitors from natural products using bioactivity screening

“…Therefore, it is of great importance to screen potential enzyme inhibitors from complex natural plants. Some emerging bioassay-guided strategies, including affinity ultrafiltration, enzyme immobilization, affinity chromatography, arise increasingly interest due to their high sensitivity and high screening efficiency [22][23][24][25]. Affinity ultrafiltration is an effective means of identifying bioactive molecules from complex matrices by using ultrafiltration to separate the target-ligand complex from the free compounds in the solution [26].…”

An Integrated Strategy for the Detection, Dereplication, and Identification of DNA-Binding Biomolecules from Complex Natural Product Mixtures

“…Whereas a detailed review of drug discovery applications using ligand fishing is beyond the scope of this discussion, 20,24 it is worth noting that this conceptual approach has been interpreted and applied in diverse ways, including within the field of natural products. 20,25−28 Notwithstanding these accounts, we noted the relative dearth of reports pertaining to the utilization of DNA as a biological target in ligandfishing-based studies despite its favorable history as a focal point for biomedical interventions.…”

“…Whereas a detailed review of drug discovery applications using ligand fishing is beyond the scope of this discussion, , it is worth noting that this conceptual approach has been interpreted and applied in diverse ways, including within the field of natural products. ,− Notwithstanding these accounts, we noted the relative dearth of reports pertaining to the utilization of DNA as a biological target in ligand-fishing-based studies despite its favorable history as a focal point for biomedical interventions. − Considering our group’s collaborative interests in the discovery of natural products that selectively inhibit different types of pediatric and triple-negative breast cancers, − we found this point intriguing given the expansive role that DNA-targeting agents have played in the field of cancer chemotherapy. − For these reasons, our goal was to develop a ligand-fishing system that could be used for the detection and identification of DNA-binding molecules from natural product mixtures. In this report, we describe our efforts to implement a natural product drug discovery pipeline using an ultrafiltration-based assay system linked with hyphenated mass spectrometry to seamlessly detect, dereplicate, and, in some cases, identify compounds from complex mixtures of natural products.…”