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

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.

journal_name

Bioorg Med Chem

authors

Crowley PJ,Berry EA,Cromartie T,Daldal F,Godfrey CR,Lee DW,Phillips JE,Taylor A,Viner R

doi

10.1016/j.bmc.2008.10.030

subject

Has Abstract

pub_date

2008-12-15 00:00:00

pages

10345-55

issue

24

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(08)00982-6

journal_volume

16

pub_type

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