Structure-Activity Relationships in Peptide Juvenoids

The structure-activity relationships for selected peptide juvenoids of the general formula R1-CONHCH(R3)CONH-C6H4-R2 were analyzed by using linear free energy relationships. It was found that both the hydrophobicity and the inductive effect of the amino-terminal substituent R1 of these compounds, quantified by the constants π and σ*, are important factors for recognition of the peptide juvenoids by their putative "target site" in the insect body and that these effects are independent of the structure of the rest of the juvenoid molecule. In contrast, the mechanism of interaction of the amino acid side chain R3 with the target site depends upon the structure of other substituents that explain the synergistic effects in juvenoid action.