Targeting Two Odorant-Binding Proteins in Acyrthosiphon pisum: Discovery of Novel Jasmone Derivatives as Aphid Repellents

Abstract

Odorant-binding proteins (OBPs) are potential targets for the discovery of insect behavior regulators. Cis-jasmone (CJ) was first identified as a repellent against Acyrthosiphon pisum (A. pisum) by its binding to ApisOBP3 and ApisOBP7. Therefore, twenty-one novel CJ derivatives were designed and synthesized based on the binding pockets of these two ApisOBPs. Almost all derivatives showed better binding affinities to ApisOBPs and aphid-repellent activities than CJ, respectively. The representative derivative 6bg had the most significant binding affinities to ApisOBP3 and ApisOBP7 with K_i values of 6.95 μM and 4.81 μM, respectively. Moreover, 6bg had the highest repellent rate of 71.62% against A.pisum at a dose of 5 μg and also elicited a dose-dependent electroantennography response. The binding mechanism revealed that hydrophobic interactions generated by nonpolar residues in ApisOBP3 and ApisOBP7 were key to the binding. This study offers insights into the rational design of novel aphid repellents targeting two OBPs.