Related Experiment Videos
Screening a natural product-based combinatorial library using FTICR mass spectrometry
Sally-Ann Poulsen1, Rohan A Davis, Timothy G Keys
1Chemical Biology Group, Eskitis Institute for Cell and Molecular Therapies, Griffith University, Nathan Campus, Brisbane 4111, Australia. s.poulsen@griffith.edu.au
Bioorganic & Medicinal Chemistry
|October 4, 2005
Summary
Researchers screened a natural product library using mass spectrometry to find inhibitors for bovine carbonic anhydrase II (bCAII). Compound 11 was identified as a potent bCAII inhibitor with a K(i) of 77.4 nM.
Area of Science:
- Biochemistry
- Natural Product Chemistry
- Analytical Chemistry
Background:
- Bovine carbonic anhydrase II (bCAII) is a key enzyme in physiological processes.
- Natural products offer a rich source for drug discovery.
- Screening diverse libraries is crucial for identifying novel enzyme inhibitors.
Purpose of the Study:
- To screen a combinatorial natural product library for bCAII inhibitors.
- To identify novel binding agents for bovine carbonic anhydrase II.
- To characterize the inhibitory potential of identified compounds.
Main Methods:
- Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) was employed for high-throughput screening.
- A combinatorial library of 11 analogues based on a fungal natural product template was synthesized.
- Competitive enzyme binding assays were used to validate mass spectrometry findings.
Main Results:
- Mass spectrometry detected a noncovalent complex between bCAII and compound 11, indicating binding.
- Compound 11, 2-(3-Chloro-4-hydroxyphenyl)-N-(4-sulfamoylphenethyl)acetamide, was identified as a tight-binding inhibitor.
- Enzyme assays confirmed compound 11's inhibitory activity with an equilibrium dissociation constant (K(i)) of 77.4 nM.
Conclusions:
- FT-ICR-MS is an effective method for screening natural product libraries for enzyme inhibitors.
- Compound 11 represents a promising lead for further investigation as a bCAII inhibitor.
- Structure-activity relationships of this natural product analogue warrant further study.