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

The relative potencies, with respect to mobilization of carbohydrates in Periplaneta americana, 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 analogues show similar time-response courses indicating that transport and degradation rates are comparable. The peptides tested fall into three distinct categories with respect to their potencies. Analogues that have single replacements at position 2 (Leu instead of Val) and 5 (Thr instead of Ser) are as active as the endogenous Periplaneta peptide. The next group shows 7-20-fold higher ED50 values; most of this lower potency can be attributed to replacements at position 7 (Ser, Gly or Asp instead of Asn) or to an lie residue at position 2 or to a combination of a Ser6 (instead of Pro) and Gly7 residue. The third group contains a Tyr at position 4 (instead of Phe) and shows a very high ED50 value or, when a Tyr4 residue is combined with an Asp7, achieves only 45% maximum activity of the native peptide, whereas all the other analogues of this study are fully efficacious.