A novel dihydroimidazoline, trans-Pro mimetic analog is a selective PK/PBAN agonist

Abstract

The pyrokinin/pheromone biosynthesis activating neuropeptide (PK/PBAN) family plays a significant role in the regulation of reproductive and developmental processes in a variety of insects. A transPro, type I beta-turn has been previously identified as important for the activity of PK/PBAN peptides. A PK/PBAN analog (PPK-Jo) incorporating a novel dihydroimidazole transPro mimetic motif was evaluated in four PK/PBAN bioassays (pheromonotropic, melanotropic, pupariation and hindgut myotropic). PPK-Jo proved to be a pure, selective melanotropic agonist in S. littoralis. The melanotropic receptor in S. littoralis demonstrates more tolerance to deviations from the ideal transPro structure than those of other PK/PBAN assays. The selective PK/PBAN agonist represents a new tool to better understand the endogenous mechanisms of these peptides and serves as a probe of the plasticity of PK/PBAN regulated systems and receptors. The dihydroimidazoline moiety is shown to function as a surrogate for a transPro in certain circumstances, and provides a novel scaffold with which to construct mimetic PK/PBAN analogs with enhanced selectivity and the potential to disrupt critical physiological processes in insect pests.