SYNTHESIS, BIOLOGICAL-ACTIVITY, AND CONFORMATIONAL STUDIES OF INSECT ALLATOSTATIN NEUROPEPTIDE ANALOGS INCORPORATING TURN-PROMOTING MOIETIES

Allatostatins are 6-18 amino acid peptides synthezed by insects to con trol production of juvenile hormones, which in turn regulate functions including metamorphosis and egg production. Four insect allatostatin neuropeptide analogues incorporating turn-promoting pseudopeptide moie ties in the region responsible for biological activity were prepared b y solid phase peptide synthetic methods. Bioassay indicated that activ ities approached those of the natural neuropeptides, and molecular mod els based on NMR data showed similar conformations and the presence of a beta-turn in the active core region for the four analogues. Differe nces in activity are believed to be due to differences in bulk and rel ative position of atoms in the unnatural portion of the analogues, and their differing degrees of conformational freedom. The studies suppor t the feasibility of development of neuropeptide-based insect control agents resistant to peptidase deactivation. (C) 1998 Published by Else vier Science Ltd. All rights reserved.