|Giard, Wilfred - UNIV DE CAEN FRANCE|
|Lange, Angela - UNIVERSITY OF TORONTO|
|Favrel, Pascal - UNIV DE CAEN FRANCE|
Submitted to: Annals of the New York Academy of Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 25, 1999
Publication Date: N/A
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 such pests. The basic premise of this research is that peptides (short chains of amino acids) serve as internal messengers in insects to regulate vital functions. Peptides themselves are unsuitable for control measures due to their instability to enzymes in the circulator and digestive systems of the insect. New, selective control measures may be developed by designing mimics of these neuropeptides that actively inhibit or stimulate functions regulated by them, resulting in disruption of the internal environment of the insect. One of the important pieces of information required to design active mimics is the identification of important parts of the peptide for biological activity. We have determined structural features of an insect neuropeptide required for induction of release of a digestive enzyme from a scallop, which serves as a good model system for other invertebrates such as insects. This led us to the development of a novel modified version of this neuropeptide that can block release of the digestive enzyme by the natural peptide. This inhibitor is a useful tool to scientists studying the digestive process in scallops and insects and may be of interest in disruption of digestion in pest insect species. Disruption of the digestive process will lead to an effective means of controlling populations of pest insects in the future.
Technical Abstract: The insect myosuppressin LMS (pGlu-Asp-Val-Asp-His-Val-Phe-Leu-Arg-Phe-NH2) elicits potent stimulation of the release of the digestive enzyme alpha-amylase from cell suspensions of the stomach-digestive gland complex of the scallop Pecten maximus. The myosuppressins are members of the FMRFamide-like peptide superfamily, which immunocytochemical data confirms is present in the scallop. Structure-activity studies indicated that the two most critical residues for bioactivity are Arg**9 and Phe**10. Bioactivity of the peptide can be maintained if the basic, aromatic residue His**5 is replaced by another basic residue (Lys) and another aromatic residue (Trp), but not the aromatic Tyr, indicating a sensitivity to the introduction of a phenolic OH group. A restricted-conformation analog containing a cyclopropyl-Ala residue in position 8 (Cpa-MS) demonstrates an ability to antagonize the amylase secretion activity of LMS at uM concentrations. This result provides evidence that the myosuppressins adopt a tight turn in the C-terminal tetrapeptide active core region while binding to the scallop digestive gland receptor. Cpa-MS may provide a useful tool to neuroendocrinologists studying in vitro and in vivo digestive processes in mollusks and other invertebrates.