A mapping of the interactions between a moth sex pheromone component and its receptor
Abstract: A number of analogues of (Z)-5-decenyl acetate (1), a pheromone component of the turnip moth, Agrotis segetum, have been synthesised and tested by using single-cell electrophysiology, in order to investigate the relationships between structure and activity, and to elucidate the interactions between 1 and its receptor. Molecular mechanics and ab initio quantum mechanical calculations have been used to provide information on molecular properties, conformational energies and electrostatic potentials, which have been used in the interpretation of the observed activities. A study of alkyl ether and enol ether analogues of 1 and (Z)-5-dodecenyl acetate (2) provides support for a previous hypothesis that the terminal chain of chain-elongated analogues of 1 adopts a loop conformation in their bioactive conformations. The acetate group of 1 has been replaced by various functional groups, which may serve as bioisosteres, to elucidate how and in what directions the acetate group interacts with the receptor site. A quantitative model, for the relationship between the activity for a large number of analogues of 1 and the structural characteristics of the analogues, was developed by using three-dimensional quantitative structure-activity relationship (3D-QSAR) methodology, including partial least square (PLS) analyses. The bioactive conformation of 1, a cisoid conformation, and the chiral recognition of the receptor was probed using constrained analogues, the enantiomers of cis- and trans-3-(4-propyl-cyclopent-2-enyl) propyl acetate.
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