Disruption of insect diapause using agonists and an antagonist of diapause hormone

Abstract

The dormant state known as diapause is widely exploited by insects to circumvent winter and other adverse seasons. For an insect to survive, feed, and reproduce at the appropriate time of year requires fine coordination of the timing of entry into and exit from diapause. One of the hormones that regulates diapause in moths is the 24-aa neuropeptide, diapause hormone (DH). Among members of the Helicoverpa/Heliothis complex of agricultural pests, DH prompts the termination of pupal diapause. Based on the structure of DH, we designed several agonists that are much more active than DH in breaking diapause. One such agonist that we describe also prevents the entry into pupal diapause when administered to larvae that are environmentally programmed for diapause. In addition, we used the unique antagonist development strategy of incorporating a dihydroimidazole ("Jones") trans-Proline mimetic motif into one of our DH agonists, thereby converting the agonist into a DH antagonist that blocks the termination of diapause. These results suggest potential for using such agents or next-generation derivatives for derailing the success of overwintering in pest species.diapause manipulation | peptidomimetics C oordinating active phases of the life cycle with seasons that provide food resources and suitable environmental conditions is crucial for sustaining viable insect populations. Major portions of the year, most notably winters in temperate zones, are unsuitable for continuous development, and most insects have evolved periods of dormancy (diapause), characterized by suppressed metabolism and bolstered stress responses that enhance survival during unfavorable seasons. Short day lengths of late summer commonly trigger the onset of diapause (1, 2), and these environmental signals prompt endocrine responses that directly initiate and eventually terminate the diapause state (3).Desynchronizing an insect pest with its appropriate seasonal diapause could be used as a tool for disrupting pest populations (4). Altering the timing of diapause has the potential to evoke ecological suicide if the insect is forced to be active during a time of year when climatic conditions are adverse or food resources are absent. Blocking entry into diapause in the autumn, breaking out of an overwintering diapause prematurely, or failing to terminate diapause at the appropriate time in the spring all have potential for desynchronizing the temporal distribution of insects. We report here the development of unique agents capable of disrupting the overwintering pupal diapause of the corn earworm, Helicoverpa zea, a member of the Heliothis/Helicoverpa complex, a worldwide group of noteworthy crop pests (5).Our target is diapause hormone (DH). This 24-aa neuropeptide, a pyrokinin in the DH-pheromone biosynthesis activating neuropeptide (PBAN) family, is best known for its action in initiating embryonic diapause in the commercial silkworm, Bombyx mori (6); however, recently, DH was also shown to exert an opposite effect in pupae of the Heliothis/Helicoverpa co...

Insect Diapause: A Review

“…In addition, the unique antagonist development strategy been designed by incorporating a dihydroimidazole ("Jones") trans-Proline mimetic motif into one of the DH agonists, thereby converting the agonist into a DH antagonist that blocks the termination of diapause. These results suggest potential for using such agents or next-generation derivatives to dismay the success of overwintering in pest species [62].…”

Functional characterization of five different PRXamide receptors of the red flour beetle Tribolium castaneum with peptidomimetics and identification of agonists and antagonists

“…The use of neuropeptidergic systems as targets for pest insect control has been a widely accepted concept and is practiced in limited cases [19, 26, 27, 29, 37, 41]. Peptidomimetics that increase stability and bioavailability have been studied for their use in pest control.…”

“…A linear PK/PBAN antagonist lead (RYF[dF]PRLa) was reported as a potent inhibitor of sex pheromone biosynthesis in Heliothis peltigera , and an analog of this lead sequence containing an appended hydrophobic group on the N-terminus demonstrates an ability to penetrate the cuticle of a heliothine insect [27]. Pupal diapause of H. zea can be disrupted using DH agonistic and/or antagonistic peptidomimetics [17, 41], and biostable analogs of the insectatachykinin, insect kinin, and pyrokinin families show aphicidal activity that match or exceed the activity of some commercially available aphicides [37]. …”

“…PK1/DH is well characterized in a number of lepidopteran insects [18]. DH induces embryonic diapause in Bombyx mori [10, 12, 39], whereas it breaks pupal diapause in heliothine moths [38, 41, 43, 44]. PK2/PBAN stimulates pheromone biosynthesis in adult female moths [34, 35].…”

Ecdysis-related pleiotropic neuropeptides expression during Anopheles albimanus development

“…37 A PK/ PBAN antagonist lead (RYF[dF]PRLa) was reported as a potent inhibitor of a sex pheromone biosynthesis in Heliothis peltigera. 38 Using a diapause hormone (DH) agonistic and/or antagonistic peptidomimetics the pupal diapause of Helicoverpa zea was disrupted 39 and analogs of the pyrokinin, insect kinin and insect tachykinin families showed aphicidal activity, that was better than some commercially available aphicides. …”