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

doi: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

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

Department of Biotechnology

Research output: Contribution to journal › Article

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 language	English
Pages (from-to)	10345-10355
Number of pages	11
Journal	Bioorganic and Medicinal Chemistry
Volume	16
Issue number	24
DOIs	https://doi.org/10.1016/j.bmc.2008.10.030
Publication status	Published - 2008 Dec 15

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All Science Journal Classification (ASJC) codes

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

Cite this

Crowley, P. J., Berry, E. A., Cromartie, T., Daldal, F., Godfrey, C. R. A., Lee, D. W., Phillips, J. E., 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, 16(24), 10345-10355. https://doi.org/10.1016/j.bmc.2008.10.030

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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.",

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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 journal › Article

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10.1016/j.bmc.2008.10.030