Binding affinity and physiological activity of some HVFLRFamide analogues on the oviducts of the locust, Locusta migratoria.

SchistoFLRFamide (PDVDHVFLRFamide) is an insect neuropeptide which inhibits spontaneous and induced contractions of locust oviduct. The active core for inhibition lies within the sequence HVFLRFamide, whereas the core for binding lies within the sequence VFLRFamide. This latter peptide shows activity reversal, possessing minor stimulatory activity. The bioassay and receptor binding assay were employed to define the relationship between the binding affinity and biological activity of HVFLRFamide analogues on the oviduct of Locusta migratoria. Each amino acid in the sequence VFLRFamide was substituted with a structurally similar or dissimilar amino acid to yield a group of HVFLRFamide analogues. These analogues were tested for their binding affinity to receptors in locust oviduct membrane and for their biological effects on contractions of the isolated locust oviduct. The results indicate that (1) with the His residue in position 1, no activity reversal is achieved, the analogues are either inhibitory or possess no biological activity; (2) the C-terminal RFamide group is critical for binding affinity and biological activity of the analogues and (3) substitution of Arg5 or Phe6 with structurally similar amino acids Lys5 or Tyr6 results in two high-affinity antagonists, while substitution of Val2 with Leu2 or Ala2 results in high-affinity agonists.