|Muren, J - STOCKHOLM UNIVERSITY|
|Isaac, R - UNIVERSITY OF LEEDS|
|Lundquist, C - STOCKHOLM UNIVERSITY|
|Nassel, D - STOCKHOLM UNIVERSITY|
Submitted to: Regulatory Peptides
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 2, 1998
Publication Date: N/A
Interpretive Summary: Insect neuropeptides are short chains of amino acids (the building blocks of proteins) that regulate a number of life processes critical for insect survival. For example, members of the insectatackykinin class of insect neuropeptides regulate muscle systems as well as digestive processes in a number of insects. Nevertheless, insect neuropeptides in and of themselves shold little promise as insect control agents because they are chemically unstable both inside insects and in the environment. Also, natural neuropeptides do not have the ability to pass through the outside skin (cuticle) of the insect. In this paper, we report on the development of insectatackykinin-like chemicals called mimics that we made in the lab and that are resistant to the processes insects normally use to degrade neuropeptides. These mimics are as active as the natural neuropeptides in affecting the ability of the insect to regulate muscle systems. This work leads us one step closer to the development of practical neuropeptide-like chemicals that will be effective in controlling certain pest insects in an environmentally friendly manner.
Technical Abstract: We are interested in the physiological roles of insect neuropeptides related to vertebrate tachykinins, such as the nine tachykinin-related peptides (TRPS) designated LemTRP 1-9, recently isolated from the cockroach, Leucophaea maderae. For in vivo studies of peptide action it is critical to reduce peptide degradation to a minimum. To obtain a TRP resistant to endo- and exoprotease-mediated hydrolysis we synthesized a peptide with one of the carboxy terminus residues substituted for a sterically hindered aminoisobutyric acid (Aib), whereas the amino terminus was blocked with a pyroglutamate. The resulting analogue of nonapeptide LemTRP I thus has the sequence pGlu-Ala-Pro-Ser-Gly-Phe-Leu-Aib-Val-Arg-NH2. This analogue was shown here to be resistant to hydrolysis by insect angiotensin-converting enzyme. Endogenous LemTRP I on the other hand was rapidly hydrolyzed by ACE at the Gly7-Val8 bond. The Aib-containing analogue has the same potency as LemTRP I in inducing contractions of the L. maderae hindgut muscle. The Aib-containing analogue (at 10 uM) was nearly as active as LemTRP I and the natural ligand locustatachykinin 1 in its ability to induce membrane depolarization in dorsal unpaired median (DUM) neurons. This enzyme-resistant TRP analogue may provide a very useful tool for future experiments on the in vivo actions of insect peptides related to the tachykinins.