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ARS Home » Plains Area » College Station, Texas » Southern Plains Agricultural Research Center » Insect Control and Cotton Disease Research » Research » Publications at this Location » Publication #316882
Title: Development of neuropeptide analogs capable of traversing the integument: A case study using diapause hormone analogs in Helicoverpa zea

Author
item ZHANG, QIRUI - The Ohio State University
item Nachman, Ronald
item KACZMAREK, KRZYSZTOF - Technical University Of Lodz
item KIERUS, KRZYSZTOF - Technical University Of Lodz
item JANUSZ, ZABROCKI - Technical University Of Lodz
item DENLINGER, DAVID - The Ohio State University

Submitted to: Journal of Insect Biochemistry and Molecular Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/26/2015
Publication Date: 12/15/2015
Citation: Zhang, Q., Nachman, R.J., Kaczmarek, K., Kierus, K., Janusz, Z., Denlinger, D.L. 2015. Development of neuropeptide analogs capable of traversing the integument: A case study using diapause hormone analogs in Helicoverpa zea. Journal of Insect Biochemistry and Molecular Biology. 67:87-93.

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, 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 penetrate the outside surface of insects. New, selective control measures may be developed by designing metabolically stable mimics of these neuropeptides that interact with the active site within the agricultural pest in such a way as to either inhibit or over-stimulate critical neuropeptide-regulated life functions. One such life function is the dormant state known as diapause, which 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. We report on the development of versions of neuropeptides of the ‘Diapause Hormone’ (DH) class with enhanced bioavailability that, unlike the natural hormone and previous modified versions, can penetrate the outer layer of corn earworm pupae and prevent them from entering the protective state of diapause. We have identified the specific structures required to penetrate the outside surface of these important plant pests. The results suggest potential for using such agents or next-generation derivatives for manipulating populations of pest species.

Technical Abstract: Diapause hormone and its analogs terminate pupal diapause in H. zea when injected, but if such agents are to be used as effective diapause disruptors it will be essential to develop simple techniques for administering active compounds that can exert their effect by penetrating the insect epidermis. In the current study, we used two molecules previously shown to have high diapause-terminating activity as lead molecules to rationally design and synthesize new amphiphilic compounds with modified hydrophobic components. An assay for diapause termination identified 13 active compounds with EC50‘s ranging from 0.9-46.0 picomole per pupa. Three compounds, Decyl-1963, Dodecyl-1967, and Heptyl-1965, selected from the 13 compounds most active in breaking diapause following injection, also successfully prevented newly-formed pupae from entering diapause when applied topically. These compounds feature straight-chain, aliphatic hydrocarbons from 7 to 12 carbons in length; DH analogs with either a short-chain length of 4 or an aromatic phenethyl group failed to act topically. Compared to a high diapause incidence of 80-90% in controls, diapause incidence in pupae receiving a 10 nmole topical application of Decyl-1963, Dodecyl-1967, or Heptyl-1965 dropped to 30-45%. Decyl-1963 and Dodecyl-1967 also remained effective when topically applied at the 1 nmole level. These results suggest the feasibility of developing DH agonists that can be applied topically and suggest the identity of new lead molecules for development of additional topically-active DH analogs. The ability to penetrate the insect epidermis and/or midgut lining is critical if such agents are to be considered for future use as pest management tools.