Chemical Biology lecture: Chemical labeling strategies to elucidate natural product structure and function
- Monday 5 July 2021
On Monday July 5th Dr. Chambers Hughes will visit our University. We are very happy that he’s willing to give an online Chemical Biology lecture during his visit. Dr. Chambers Hughes works at the Interfaculty Institute of Microbiology and Infection Medicine at the University of Tübingen. The Hughes Research Group specializes in microbial natural product discovery, synthesis, and chemical biology. They have characterized scores of natural products using a combination of NMR spectroscopy and mass spectrometry, they have completed several total syntheses and they have identified the cellular targets of numerous secondary metabolites.
Biologically-active natural products (NPs) have historically been isolated from plant or microbial extracts on the basis of their biological activity, which is evaluated using a bioassay. This approach, which has yielded thousands of bioactive NPs and scores of NP-based drugs, is largely disconnected from any consideration of chemical structure. It is now well known that certain naturally-occurring chemical moieties or substructures, such as β-lactams, β-lactones, and phosphonates, are closely associated with biological activity. These moieties can be specifically targeted in extracts using reagents that label them with a high degree of chemoselectivity. The reagents or “probes” are designed to have prominent UV/vis properties, high ionization efficiency, distinct isotopic features, and conspicuous reagent-specific MS/MS fragments such that the labeled compounds are readily detected using standard LC-MS instrumentation.
To date, we have designed and applied probes that target NPs with electrophilic moieties (epoxides, α,β-unsaturated carbonyl groups, β-lactones, β-lactams), conjugated alkenes, terminal alkynes, enediynes, isocyanides, phosphonates, and amino groups. We have also designed reagents that facilitate crystallography-based structure elucidation. Here, chemical labeling produces derivatives with superior crystallinity when compared to the unlabeled compounds and so aids in the process of obtaining crystals for X-ray and electron diffraction experiments.