POTENT PHEROMONOTROPIC MYOTROPIC ACTIVITY OF A CARBORANYL PSEUDOTETRAPEPTIDE ANALOG OF THE INSECT PYROKININ/PBAN NEUROPEPTIDE FAMILY ADMINISTERED VIA INJECTION OR TOPICAL APPLICATION/

A pseudotetrapeptide analogue of the pyrokinin/PBAN or FXPRLamide fami ly (Cbe-Thr-Pro-Arg-Leu-NH2; Cbe = 2-o-carboranylethanoyl-), in which the phenyl ring of the Phe side chain is replaced with the hydrophobic cage-like o-carborane moiety, was synthesized and found to be 10-fold more potent than cockroach leucopyrokinin on an isolated cockroach hi ndgut bioassay system. In contrast with the naturally occurring peptid e, the myostimulatory activity could not be immediately reversed follo wing a saline rinse, providing evidence that the pseudopeptide analogu e binds very strongly to the receptor. Once the analogue reaches the r eceptor, strong receptor binding characteristics may allow it to avoid inactivation by hemolymph peptidases. Although it has an eightfold sm aller sequence than the endogenous 33-membered pheromone biosynthesis activating neuropeptide (PBAN), the carboranyl analogue is 10-fold mor e potent in an in vivo pheromonotropic bioassay of the female tobacco budworm moth Heliothis virescens, demonstrating that the small, C-term inal pentapeptide pyrokinin core analogue contains all the structural information necessary to fully activate pyrokinin receptors. In contra st with PBAN, the amphiphylic carboranyl analogue elicits pheromone pr oduction following topical application in aqueous solution to the late ral abdominal surface of H. virescens. providing a noninvasive means o f inducing pheromone production in moths. The analogue can potentially serve as a useful tool to insect researchers studying, and/or attempt ing to disrupt, physiological processes regulated by pyrokinin-like ne uropeptides in insects. A possible role for this and related pyrokinin analogues in future pest insect management strategies is briefly disc ussed.