Date: 01.12.2022

Species-selective peptidic agonists of the juvenile hormone receptor

Peptidic analogs of the juvenile hormone (JH) selectively interfere with development of linden bugs. Newly derived peptidic juvenoids bind and activate the JH receptor of the linden bug at picomolar doses, thus by far surpassing potency of the native linden bug hormone.

Image description: Left: Models of the JH receptor binding pocket containing the native hormone (top) and peptidic juvenoid (bottom) reveal increased number of contacts in the latter (image: Roman Tuma). Right: The color pattern on the adult linden bug was chosen for the cover of PNAS that features the corresponding article by Sarka Tumova and colleagues (photo: Matej Milacek).

Synthetic mimics of the insect juvenile hormone (JH) exemplify biorational pesticides. Unique peptidic juvenoids with target-species specific effects were discovered in the early 1970s. However, these promising compounds were abandoned with their mode of action never addressed. Our study shows that peptidic juvenoids act through the canonical JH receptor signaling to affect development and reproduction of the target insect. Our newly synthesized peptidic derivatives outperform established JH mimics by two orders of magnitude while retaining their target species selectivity. We further propose an advanced structural model for interaction of these highly potent agonists with the JH receptor. These results unveil the potential of peptidic juvenoids as agents for precisely targeted and sustainable insect control.

Tumova, S., Milacek, M., Snajdr, I., Muthu, M., Tuma, R., Reha, D., Jedlicka, P., Bittova, L., Novotna, A., Majer, P., Sedlak, D., Jindra, M. (2022) Unique peptidic agonists of a juvenile hormone receptor with species-specific effects on insect development and reproduction. Proceedings of the National Academy of Sciences U.S.A. 119, e2215541119.






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