|Nachman, Ronald - Ron|
Submitted to: Peptides
Publication Type: Peer reviewed journal
Publication Acceptance Date: 10/9/2007
Publication Date: 2/15/2008
Citation: Kim, Y., Nachman, R.J., Aimanova, K., Gill, S., Adams, M.E. 2008. The pheromone biosynthesis activating neuropeptide (PBAN) receptor of Heliothis virescens: Identification, functional expression, and structure-activity relationships of ligand analogs. Peptides. 29:268-275. Interpretive Summary: Because of problems with the development of resistance to conventional pesticides, there is a critical need for new concepts and alternative approaches in controlling insect pests. The basic premise of this research is that neuropeptides (short chains of amino acids) serve as potent messengers in insects to regulate vital functions. Nevertheless, these neuropeptides in and of themselves hold little promise as pest control agents because of susceptibility to being degraded in the target pest, and inability to pass through the outside skin (cuticle) and/or digestive tract. We must design neuropeptide mimics that resist degradation by enzymes in the digestive tract and blood of pest insects and interact with the active site within the agricultural pest in such a way as to either over-activate or block critical, neuropeptide-regulated life functions. We report on the isolation, identification and characterization of the active site for a member of the pyrokinin class of neuropeptides known as PBAN from the moth Heliothis virescens, an important agricultural pest. In moths, PBAN regulates the release of sex pheromones, critical for reproduction. This discovery will aid in the design of neuropeptide-like compounds capable of disrupting the reproduction and propagation of these and related moths. The work brings us one step closer to the development of practical neuropeptide-like substances that will be effective in controlling pest insects in an environmentally friendly fashion.
Technical Abstract: Pheromone biosynthesis activating neuropeptide (PBAN) promotes synthesis and release of sex pheromones in moths. We have identified and functionally expressed a PBAN receptor from Heliothis virescens (HevPBANR) and elucidated structure-activity relationships of PBAN analogs. Screening of a larval CNS cDNA library revealed three putative receptor subtypes and nucleotide sequence comparisons suggest they are produced through alternative splicing at the 3’-end. RT-PCR amplified preferentially HevPBANR-C from female pheromone glands. CHO cells expressing HevPBANR-C are highly sensitive to PBAN and related analogs, especially those sharing the C-terminal pentapeptide core, FXPRLamide (X = T, S or V). Alanine replacements in the C-terminal hexapeptide (YFTPRLamide) revealed the relative importance of each residue in the active core as follows, R5, L6, F2, P4, T3, and Y1. This study provides a framework for the rational design of PBANR-specific agonists and/or antagonists that could be exploited for disruption of reproductive function in agriculturally important insect pests.