The role of molecular modeling in the design of analogues of the fungicidal natural products crocacins A and D

Patrick J. Crowley, Edward A. Berry, Thomas Cromartie, Fevzi Daldal, Christopher R.A. Godfrey, Dong Woo Lee, Janet E. Phillips, Anne Taylor, Russell Viner

Research output: Contribution to journalArticle

30 Citations (Scopus)

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 bc 1 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 bc 1 complex, which validated the binding model and which confirmed that the crocacins are a new class of inhibitor of the cytochrome bc 1 complex.

Original languageEnglish
Pages (from-to)10345-10355
Number of pages11
JournalBioorganic and Medicinal Chemistry
Volume16
Issue number24
DOIs
Publication statusPublished - 2008 Dec 15

Fingerprint

Molecular modeling
Cytochromes
Biological Products
Respiration
Beef
Pathogens
Chickens
Assays
Crystal structure
crocacin D
crocacin A

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Crowley, Patrick J. ; Berry, Edward A. ; Cromartie, Thomas ; Daldal, Fevzi ; Godfrey, Christopher R.A. ; Lee, Dong Woo ; Phillips, Janet E. ; Taylor, Anne ; Viner, Russell. / The role of molecular modeling in the design of analogues of the fungicidal natural products crocacins A and D. In: Bioorganic and Medicinal Chemistry. 2008 ; Vol. 16, No. 24. pp. 10345-10355.
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Crowley, PJ, Berry, EA, Cromartie, T, Daldal, F, Godfrey, CRA, Lee, DW, Phillips, JE, Taylor, A & Viner, R 2008, 'The role of molecular modeling in the design of analogues of the fungicidal natural products crocacins A and D', Bioorganic and Medicinal Chemistry, vol. 16, no. 24, pp. 10345-10355. https://doi.org/10.1016/j.bmc.2008.10.030

The role of molecular modeling in the design of analogues of the fungicidal natural products crocacins A and D. / Crowley, Patrick J.; Berry, Edward A.; Cromartie, Thomas; Daldal, Fevzi; Godfrey, Christopher R.A.; Lee, Dong Woo; Phillips, Janet E.; Taylor, Anne; Viner, Russell.

In: Bioorganic and Medicinal Chemistry, Vol. 16, No. 24, 15.12.2008, p. 10345-10355.

Research output: Contribution to journalArticle

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