A novel dihydroimidazoline, trans-Pro mimetic analog is a selective PK/PBAN agonist.
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.
Nachman
Ronald J
RJ
US Department of Agriculture, Areawide Pest Management Research, Southern Plains Agricultural Research Center, College Station, TX 77845, USA. nachman@tamu.edu
Ben Aziz
Orna
O
Davidovitch
Michael
M
Kaczmarek
Krzysztof
K
Zabrocki
Janusz
J
Williams
Howard
H
Strey
Allison
A
Altstein
Miriam
M
D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D048288:Imidazolines / Q000737:chemistry*; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D007313:Insecta / Q000378:metabolism*; D007814:Larva / Q000187:drug effects / Q000378:metabolism; D008958:Models, Molecular; D018716:Molecular Mimicry; D009119:Muscle Contraction / Q000187:drug effects; D009479:Neuropeptides / Q000819:agonists*; D010675:Pheromones / Q000096:biosynthesis; D017433:Protein Structure, Secondary / Q000235:genetics; D011979:Receptors, Pituitary Hormone / Q000378:metabolism
D048288:Imidazolines; D019476:Insect Proteins; D009479:Neuropeptides; D010675:Pheromones; D011979:Receptors, Pituitary Hormone; C079709:pheromone biosynthesis activating neuropeptide, Helicoverpa zea; C029446:MSH receptor