Submitted to: Proc Intl Sym on Molecular Mech. of Insect Metamorphosis & Diapause
Publication Type: Book / Chapter
Publication Acceptance Date: 2/16/1996
Publication Date: N/A
Citation: N/A Interpretive Summary:
Technical Abstract: Members of the pyrokinin/PBAN/diapause induction neuropeptide family share the common C-terminal pentapeptide Phe-X-Pro-Arg-Leu-NH2 and influence hindgut and oviduct contraction, pheromone biosynthesis, diapause induction and melanization in a variety of insect species. Molecular dynamics and NMR analysis of a rigid, cyclic pyrokinin analog reveal the presence of a beta-turn conformation over residues X-Pro-Arg-Leu in the C-terminal pentapeptide active core. Pseudodipeptide analogs containing carbocyclic Pro-mimetic moieties, feature a reverse peptide bond and a hydrogen bond that promotes the formation of a turn in the analogous region of the analog. Superimposition of the 6-membered carbocyclic pseudopeptide analog onto the beta-turn of the rigid, cyclic analog indicate that the acyl substituents on the carbocyclic ring adopt a diequatorial, rather than a diaxial, orientation during receptor interaction. The 5-membered carbocyclic pseudopeptide analog rPbm-tCpd-Arg-Leu-NH2 approached the myostimulatory potency of the parent pentapeptide on the isolated cockroach hindgut assay. Replacement of the phenyl ring of the Phe residue of the pentapeptide core with the hydrophobic, ball-shaped o-carborane moiety led to a pseudotetrapeptide analog that demonstrated high potency in cockroach hindgut myotropic, silkworm diapause induction, and tobacco budworm moth pheromonotropic assays.