STRUCTURE-ACTIVITY-RELATIONSHIPS FOR THE LIPID-MOBILIZING ACTION OF FURTHER BIOANALOGS OF THE ADIPOKINETIC HORMONE RED PIGMENT-CONCENTRATING HORMONE FAMILY OF PEPTIDES

The relative potencies, with respect to mobilization of lipids in Locusta migratoria, of nine synthetic bioanalogues (naturally-occurring members of the adipokinetic hormone/red pigment-concentrating hormone family of peptides) and of one synthetic analogue have been assessed by measuring complete dose-response curves. All peptides show similar time-response curves; a clear indication of comparable transport and degradation rates. From the dose-response curves of the bioanalogues tested in this study four distinct activity groups with respect to potencies and/or maximal activities can be distinguished. Three octapeptides, the hypertrehalosaemic peptide from Tenebrio molitor and the adipokinetic peptides from Empusa pennata and Libellula auripennis, which have replacements at positions 5, 2, and 2 and 7, respectively, compared to locust adipokinetic hormone I, have 4-7-fold higher ED50 values. The next group which has about 50-fold higher ED50 values consists of the hypertrehalosaemic peptides from Phormia terraenovae and Heliothis zea. The lower potencies are attributed mainly to changes at positions 3 and 6, to the charged aspartic residue at position 7 and to the substitution at position 10 in the decapeptide. The third group has very high ED50 values. This is attributed to the isoleucine residue at position 2 in the hypertrehalosaemic peptide from Polyphaga aegyptiaca and to the tyrosine residue at position 4 in the Melolontha-analogue peptide. The fourth group is made up of three peptides: the peptide from Melolontha melolontha, which contains a charged aspartic acid at position 7 in addition to the tyrosine residue at position 4, as well as the adipokinetic and hypotrehalosaemic peptides of Tabanus atratus do not have more than 50 or 70%, respectively, of the maximal possible activity, whereas all other analogues of this study reach full efficacy. The Melolontha peptide and the Tabanus hypotrehalosaemic peptide are not able to reduce the lipid mobilizing response to co-injected Locusta adipokinetic hormone I. However, co-injections of Tabanus adipokinetic peptide and Locusta adipokinetic hormone II show that these peptides apparently bind to the native peptide II receptor subtype, whereas such co-injections demonstrate that this is not the case for the Melolontha corpus cardiacum peptide.