In vivo structure–activity studies on the dark‐color‐inducing neurohormone of locusts

In the 11‐residue long dark‐color‐inducing neurohormone (DCIN = [His⁷]‐corazonin), of locusts, from residue 2 to residue 11, one amino acid at each time was substituted by d ‐phenylalanine (d ‐Phe). The dark‐color‐inducing effect of these peptides was investigated in comparison with unaltered DCIN by a bioassay based on nymphs of a DCIN‐deficient albino mutant of the migratory locust, Locusta migratoria. Substitution of any single amino acid by d ‐Phe always reduced the activity, but did not abolish it completely. Maximum inactivation was obtained after substitution of Gln4, Ser6, or Trp9. The latter two residues are within the partial sequence ‐Ser‐Xxx‐Gly‐Trp‐ (Xxx = His in the DCIN) that seems to be important for the dark‐color‐inducing activity, as found also in another study (Insect Biochem. Mol. Biol. 32, 2002, 909). Gln4, however, is outside of this partial sequence. Minimal, although still considerable, inactivation occurred after substitution of Gly8, Phe3, or Asn11, despite the fact that Gly8 is within the ‐Ser‐Xxx‐Gly‐Trp‐ partial sequence. In conclusion, no single active core was found, indicating that the whole sequence of the DCIN is necessary to induce maximum darkening effect. No difference was found in the activity of the peptides in which Gly8 was substituted by d ‐Phe or by L ‐Phe. Therefore the ‐Ser‐Xxx‐Gly‐Trp‐ partial sequence does not seem to be stabilized by a type II β‐turn. Nevertheless, existence of another kind of turn that includes this partial sequence is feasible. A single unsuccessful attempt was made to discover an antagonist to the DCIN.