Ketomethylene and Methyleneamino Pseudopeptide Analogues of Insect Allatostatins Inhibit Juvenile Hormone and Vitellogenin Production in the Cockroach Blattella germanica

Abstract

Metabolic studies on insect allatostatins have suggested that the dipeptide Leu-Tyr may be a target for endopeptidases. In order to increase resistance to degradation, methyleneamino Ψ[CH 2NH] and ketomethylene Ψ[COCH 2] peptide bond surrogates have been introduced at the position Leu 3-Tyr 4 of the allatostatin Asp-Arg-Leu-Tyr-Ser-Phe-Gly-Leu-amide (BLAST-2), and Leu 3-Phe 4 of [Phe 4]BLAST-2, respectively. Assays of inhibition of juvenile hormone (JH) synthesis in vitro by corpora allata from the cockroach Blattella germanica showed that both analogues were similarly active to the respective model peptides. The methyleneamino analogue was further tested in vivo as an inhibitor of JH synthesis, and in vivo and in vitro as an inhibitor of vitellogenin production by the fat body of B. germanica. The analogue was less active than BLAST-2 when tested in vitro, but more active than it when tested in vivo.