An aminoisobutyric acid-containing analogue of the cockroach tachykinin-related peptide, LemTRP-1, with potent bioactivity and resistance to an insect angiotensin-converting enzyme.

Nine tachykinin-related peptides (TRPs), designated LemTRP-1-9, were recently isolated from the cockroach, Leucopheae maderae. To obtain a LemTRP 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) and with the amino terminus blocked with a pyroglutamate. The Aib-containing analogue of the nonapeptide LemTRP-1 (Aib-LemTRP-1) thus has the sequence pGlu-Ala-Pro-Ser-Gly-Phe-Leu-Aib-Val-Arg-NH2. This analogue was shown to be resistant to hydrolysis by recombinant angiotensin-converting enzyme (ACE), from Drosophila melanogaster. Endogenous LemTRP-1 on the other hand was rapidly hydrolysed by ACE at the Gly7-Val8 bond, resulting in a single heptapeptide. The Aib-LemTRP-1 has about the same potency as LemTRP-I in inducing contractions of the L. maderae hindgut muscle. It was also tested in intracellular recordings for ability to induce firing of action potentials in dorsal unpaired median (DUM) neurons in the metathoracic ganglion of the locust Locusta migratoria. The Aib-containing analogue was nearly as active as LemTRP-1 and the natural ligand locustatachykinin I. LemTRP-1 and Aib-LemTRP-1 had the same transient time course of action on the cockroach hindgut. This suggests that peptide degradation is not likely to be the cause of the transient action of TRPs.