Effects of carboxyl and acylamino linkers in synthetic derivatives of aphid alarm pheromone (E)-β-farnesene on repellent, binding and aphicidal activity

Abstract

Insect odorant-binding proteins (OBPs) have significant roles in the transmission of semiochemical signals. In our previous study, a series of salicylate-substituted carboxyl (E)-β-farnesene (EBF) derivatives were synthesized with a carboxyl linker to bridge the EBF geranyl chain with salicylate aromatic group, and their binding mechanism with aphid OBPs was studied. In present study, to clarify the effects of linkers on the bioactivities of salicylate-substituted EBF derivatives against the aphid, a new series of salicylate-substituted EBF derivatives with an acylamino linker was designed and synthesized by the bioisosterism strategy. Their aphid-repellent activities, binding mechanisms with aphid OBPs, and aphicide activities were compared. The bioassay results indicated that salicylate-substituted EBF derivatives with a carboxyl linker showed higher aphid-repellent and OBP binding activities than the derivatives with an acylamino-linker. The molecular dynamic simulations and MM/GBSA calculation suggested that a more excellent hydrophobic linker such as carboxyl linker was essential for binding activity due to its stronger interactions with surrounding amino acids of the target proteins. Nevertheless, the salicylate substituted EBF derivatives with an acylamino linker exhibited significantly higher aphicidal activities than those with a carboxyl linker. In addition, the scaffold structure of EBF was essential to maintain the inherent aphid-repellent activity, target OBPs binding, and aphicidal activity. This work provides valuable guidelines for the rational design of different aphid control agents.