PSEUDODIPEPTIDE ANALOGS OF THE PYROKININ PBAN (FXPRLA) INSECT NEUROPEPTIDE FAMILY CONTAINING CARBOCYCLIC PRO-MIMETIC CONFORMATIONAL COMPONENTS/

Three N-terminal amino acid residues of the C-terminal core pentapepti de Phe-X-Pro-Arg-Leu-NH2 (X = Gly, Ser, Thr, Val) of the pryokinin/PBA N insect neuropeptide family were replaced by nonpeptide moieties. To reestablish some of the conformational properties lost upon removal of the peptide bonds and Pro of the three amino acid residue block, carb ocyclic Pro-mimetic components were incorporated into pseudodipeptide analogs. The most active analog contained a trans-DL-1,2-cyclopentaned icarboxyl carbocyclic component and proved to be over 3 orders of magn itude more potent than a simple, straight chain pseudodipeptide analog and approached the potency of the pentapeptide core in a cockroach hi ndgut myotropic bioassay. The pseudodipeptide analog retains a critica l carbonyl residue which can participate in a hydrogen bond that stabi lizes a beta-turn conformation in the active core region of the pyroki nin/PBAN peptides. This study demonstrates that knowledge of active co nformation can be used to enhance the biological potency of pseudopept ide mimetic analogs of insect neuropeptides. The analogs represent a m ilestone in the development of pseudopeptide and nonpeptide mimetic an alogs of this peptide family, which has been associated with such crit ical physiological processes as hindgut and oviduct contraction, phero mone biosynthesis, diapause induction, and induction of melanization a nd reddish coloration in a variety of insects. Mimetic analogs are pot entially valuable tools to insect neuroendocrinologists studying these physiological processes and/or engaged in the development of future p est management strategies.