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 | |
| 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
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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
TY - JOUR
T1 - The role of molecular modeling in the design of analogues of the fungicidal natural products crocacins A and D
AU - Crowley, Patrick J.
AU - Berry, Edward A.
AU - Cromartie, Thomas
AU - Daldal, Fevzi
AU - Godfrey, Christopher R.A.
AU - Lee, Dong Woo
AU - Phillips, Janet E.
AU - Taylor, Anne
AU - Viner, Russell
PY - 2008/12/15
Y1 - 2008/12/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=56649111202&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=56649111202&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2008.10.030
DO - 10.1016/j.bmc.2008.10.030
M3 - Article
C2 - 18996700
AN - SCOPUS:56649111202
VL - 16
SP - 10345
EP - 10355
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 24
ER -