Abstract
Extensive molecular modeling based on crystallographic data was used to aid the design of synthetic analogues of the fungicidal naturally occurring respiration inhibitors crocacins A and D, and an inhibitor binding model to the mammalian cytochrome bc1 complex was constructed. Simplified analogues were made which showed high activity in a mitochondrial beef heart respiration assay, and which were also active against certain plant pathogens in glasshouse tests. A crystal structure was obtained of an analogue of crocacin D bound to the chicken heart cytochrome bc1 complex, which validated the binding model and which confirmed that the crocacins are a new class of inhibitor of the cytochrome bc1 complex.
Original language | English |
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Pages (from-to) | 10345-10355 |
Number of pages | 11 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 16 |
Issue number | 24 |
DOIs | |
Publication status | Published - 2008 Dec 15 |
All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry