| Title: | "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" |
| Author(s): | Nachman RJ; Kim YJ; Wang XJ; Etzkorn FA; Kaczmarek K; Zabrocki J; Adams ME; |
| Address: | "Areawide Pest Management Research, Southern Plains Agricultural Research Center, USDA, 2881 F/B Road, College Station, TX 77845, USA. nachman@tamu.edu" |
| DOI: | 10.1016/j.bmc.2009.03.036 |
| ISSN/ISBN: | 1464-3391 (Electronic) 0968-0896 (Linking) |
| Abstract: | "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" |
| Keywords: | Alkenes/chemical synthesis/chemistry/pharmacology Amino Acid Sequence Animals CHO Cells Cell Line Cricetinae Cricetulus Insecticides/chemical synthesis/*chemistry/pharmacology Lepidoptera/drug effects Molecular Sequence Data Neuropeptides/*chemistry/pharm; |
| Notes: | "MedlineNachman, Ronald J Kim, Young-Joon Wang, Xiaodong J Etzkorn, Felicia A Kaczmarek, Krzysztof Zabrocki, Janusz Adams, Michael E eng R01 GM067310/GM/NIGMS NIH HHS/ GM 067310/GM/NIGMS NIH HHS/ R01 GM63271-01/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural England 2009/04/10 Bioorg Med Chem. 2009 Jun 15; 17(12):4216-20. doi: 10.1016/j.bmc.2009.03.036. Epub 2009 Mar 25" |
