Structural highlights
Function
[ACHP_LYMST] Binds to acetylcholine. Modulates neuronal synaptic transmission.
Publication Abstract from PubMed
The development of novel and safe insecticides remains an important need for a growing world population to protect crops and animal and human health. New chemotypes modulating the insect nicotinic acetylcholine receptors have been recently brought to the agricultural market, yet with limited understanding of their molecular interactions at their target receptor. Herein, we disclose the first crystal structures of these insecticides, namely, sulfoxaflor, flupyradifurone, triflumezopyrim, flupyrimin, and the experimental compound, dicloromezotiaz, in a double-mutated acetylcholine-binding protein which mimics the insect-ion-channel orthosteric site. Enabled by these findings, we discovered novel pharmacophores with a related mode of action, and we describe herein their design, synthesis, and biological evaluation.
Structural Biology-Guided Design, Synthesis, and Biological Evaluation of Novel Insect Nicotinic Acetylcholine Receptor Orthosteric Modulators.,Montgomery M, Rendine S, Zimmer CT, Elias J, Schaetzer J, Pitterna T, Benfatti F, Skaljac M, Bigot A J Med Chem. 2022 Jan 5. doi: 10.1021/acs.jmedchem.1c01767. PMID:34986308[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Montgomery M, Rendine S, Zimmer CT, Elias J, Schaetzer J, Pitterna T, Benfatti F, Skaljac M, Bigot A. Structural Biology-Guided Design, Synthesis, and Biological Evaluation of Novel Insect Nicotinic Acetylcholine Receptor Orthosteric Modulators. J Med Chem. 2022 Jan 5. doi: 10.1021/acs.jmedchem.1c01767. PMID:34986308 doi:http://dx.doi.org/10.1021/acs.jmedchem.1c01767
