Discovering allatostatin type-C receptor specific agonists.

Autor: Kahveci K; Department of Molecular Biology and Genetics, Boğaziçi University, İstanbul, Türkiye., Düzgün MB; Department of Molecular Biology and Genetics, Boğaziçi University, İstanbul, Türkiye., Atis AE; Plant Protection Product and Toxicology Department, Plant Protection Central Research Institute, Ankara, Türkiye., Yılmaz A; Plant Protection Product and Toxicology Department, Plant Protection Central Research Institute, Ankara, Türkiye., Shahraki A; Department of Molecular Biology and Genetics, Boğaziçi University, İstanbul, Türkiye.; Kolb Lab, Department of Pharmacy, The Philipp University of Marburg, Marburg, Germany., Coskun B; Plant Protection Product and Toxicology Department, Plant Protection Central Research Institute, Ankara, Türkiye., Durdagi S; Molecular Therapy Lab, Department of Pharmaceutical Chemistry, School of Pharmacy, Bahçeşehir University, İstanbul, Türkiye. serdar.durdagi@bau.edu.tr.; Computational Biology and Molecular Simulations Laboratory, Department of Biophysics, School of Medicine, Bahçeşehir University, İstanbul, Türkiye. serdar.durdagi@bau.edu.tr.; Lab for Innovative Drugs (Lab4IND), Computational Drug Design Center (HITMER), Bahçeşehir University, İstanbul, Türkiye. serdar.durdagi@bau.edu.tr., Birgul Iyison N; Department of Molecular Biology and Genetics, Boğaziçi University, İstanbul, Türkiye. birgul@bogazici.edu.tr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 May 10; Vol. 15 (1), pp. 3965. Date of Electronic Publication: 2024 May 10.
DOI: 10.1038/s41467-024-48156-w
Abstrakt: Currently, there is no pesticide available for the selective control of the pine processionary moth (Thaumetopoea pityocampa-specific), and conventional methods typically rely on mechanical techniques such as pheromone traps or broad-spectrum larvicidal chemicals. As climate change increases the range and dispersion capacity of crop and forest pests, outbreaks of the pine processionary occur with greater frequency and significantly impact forestry and public health. Our study is carried out to provide a T. pityocampa-specific pesticide targeting the Allatostatin Type-C Receptor (AlstR-C). We use a combination of computational biology methods, a cell-based screening assay, and in vivo toxicity and side effect assays to identify, for the first time, a series of AlstR-C ligands suitable for use as T. pityocampa-specific insecticides. We further demonstrate that the novel AlstR-C targeted agonists are specific to lepidopteran larvae, with no harmful effects on coleopteran larvae or adults. Overall, our study represents an important initial advance toward an insect GPCR-targeted next-generation pesticide design. Our approach may apply to other invertebrate GPCRs involved in vital metabolic pathways.
(© 2024. The Author(s).)
Databáze: MEDLINE
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