Aib-Containing Analogues of the Insect Kinin Neuropeptide Family Demonstrate Resistance to an Insect Angiotensin-Converting Enzyme and Potent Diuretic Activity

Abstract

Nachman, R. J., R. E. Isaac, G. M. Coast and G. M. Holman. Aib-containing analogues of the insect kinin neuropeptide family demonstrate resistance to an insect angiotensin-converting enzyme and potent diuretic activity. Peptides 18(1) 53–57, 1997.—Analogues of the insect kinin family in which the Xaa 2 residue of the C-terminal pentapeptide core sequence Phe-Xaa 1-Xaa 2-Trp-Gly-NH 2 (Xaa 1 = Asn, His, Phe, Ser, or Tyr; Xaa 2 = Ala, Ser, or Pro) is replaced with sterically hindered aminoisobutyric acid (Aib) prove to be resistant to hydrolysis by housefly ( Musca domestica) angiotensin-converting enzyme (ACE), an endopeptidase capable of hydrolysis and inactivation of the naturally occurring insect kinin peptides. The Aib residue is compatible with formation of a turn in the active core region that is important for the biological activity of the insect kinins. One of the Aib-containing analogues, pGlu-Lys-Phe-Phe-Aib-Trp-Gly-NH 2, is five- and eightfold more active than the most active endogenous insect kinins in cockroach ( Leucophaea maderae) hindgut myotropic and cricket ( Acheta domesticus) Malpighian tubule fluid secretion assays, respectively. As the analogue is blocked at both the amino- and the carboxyl-terminus and resistant to an endopeptidase present in insects, it is better adapted than the endogenous peptides to survive for long periods in the hemolymph. Enzyme-resistant insect kinin analogues can provide useful tools to insect researchers studying the neuroendocrine control of water and ion balance and the physiological consequences of challenging insects with diuretic factors that demonstrate enhanced resistance to peptidase attack. If these analogues, whether in isolation or in combination with other factors, can disrupt the water and/or ion balance, they hold potential utility for the control of pest insect populations in the future.