Potent activity of a PK/PBAN analog with an (E)-alkene, trans-Pro mimic identifies the Pro orientation and core conformation during interaction with HevPBANR-C receptor.
The pyrokinin/pheromone biosynthesis activating neuropeptide (PK/PBAN) family plays a multifunctional role in an array of important physiological processes in insects, including regulation of sex pheromone biosynthesis in moths. A cyclic PK/PBAN analog (cyclo[NTSFTPRL]) retains significant activity on the pheromonotropic HevPBANR receptor from the tobacco budworm Heliothis virescens expressed in CHO-K1 cells. Previous studies indicate that this rigid, cyclic analog adopts a type I beta-turn with a transPro over residues TPRL within the core PK/PBAN region. An analog containing an (E)-alkene, trans-Pro mimetic motif was synthesized, and upon evaluation on the HevPBANR receptor found to have an EC(50) value that is not statistically different from a parent C-terminal PK/PBAN hexapeptide sequence. The results, in aggregate, provide strong evidence for the orientation of Pro and the core conformation of PK/PBAN neuropeptides during interaction with the expressed PBAN receptor. The work further identifies a novel scaffold with which to design mimetic PBAN analogs as potential leads in the development of environmentally favorable pest management agents capable of disrupting PK/PBAN-regulated pheromone signaling systems.
Nachman
Ronald J
RJ
Areawide Pest Management Research, Southern Plains Agricultural Research Center, USDA, 2881 F/B Road, College Station, TX 77845, USA. nachman@tamu.edu
Kim
Young-Joon
YJ
Wang
Xiaodong J
XJ
Etzkorn
Felicia A
FA
Kaczmarek
Krzysztof
K
Zabrocki
Janusz
J
Adams
Michael E
ME
D000475:Alkenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D007306:Insecticides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007915:Lepidoptera / Q000187:drug effects; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000737:chemistry* / Q000494:pharmacology; D011392:Proline / Q000737:chemistry*; D011485:Protein Binding; D018013:Receptors, Neuropeptide / Q000737:chemistry* / Q000378:metabolism; D014162:Transfection
D000475:Alkenes; D007306:Insecticides; D009479:Neuropeptides; D018013:Receptors, Neuropeptide; C079709:pheromone biosynthesis activating neuropeptide, Helicoverpa zea; C079229:pyrokinin; D011392:Proline