Odorant-Binding Protein 3-Oriented Rational Design and Discovery of Novel Jasmonate Derivatives as Potential Aphid-Repellent Agents

Odorant-binding protein (OBP) is a potential target for developing insect behavior control agents due to its properties in transporting semiochemicals. In this study, 12 novel jasmonic acid (JA) derivatives were rationally designed and synthesized based on the binding features between Acyrthosiphon pisum OBP3 (ApisOBP3) and compound D1 [(E)-3,7-dimethylocta-2,6-dien-1-yl 2-(3-oxo-2-pentylcyclopentyl)acetate] with a binding affinity (Kd) of 26.79 μM. Most novel JA derivatives displayed better binding affinities than D1 (Kd = 1–26 μM). Among them, compound 6b [(E)-3,7-dimethylocta-2,6-dien-1-yl-2-((Z)-3-((acryloyloxy)imino)-2-pentylcyclopentyl)acetate] is the most promising compound with an excellent Kd of 1.33 μM and a significant repellent activity with repellent rates of 50–60% against A. pisum and Myzus persicae. Both hydrophobic and electrostatic interactions were found to contribute significantly to the binding of 6b to ApisOBP3. This study provides significant guidance for the rational design and efficient identification of novel aphid repellents based on aphid OBPs.