ArticleProceedings of the National Academy of Sciences of the United States of America2010
Nicotinic pharmacophore: the pyridine N of nicotine and carbonyl of acetylcholine hydrogen bond across a subunit interface to a backbone NH.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 100 citations in OpenAlex.
- Understanding varenicline function via key receptor and ligand interactions.Cell reports. Physical science · 2025Article
- Pro-angiogenic potential of the isoxazole derivative ISO-1 via α7-nAChRs activation in human endothelial cells.Biomedical reports · 2025Article
- A single main-chain hydrogen bond required to keep GABANature communications · 2025Article
- A Pharmacophore for Drugs Targeting the α4α4 Binding Site of the (α4)Journal of neurochemistry · 2025Article
- Article
- Genetic Code Expansion for Mechanistic Studies in Ion Channels: An (Un)natural Union of Chemistry and Biology.Chemical reviews · 2024Review
- Expression and purification of fluorinated proteins from mammalian suspension culture.Methods in enzymology · 2024Article
- Electrostatic Contributions to the Binding Free Energy of Nicotine to the Acetylcholine Binding Protein.The journal of physical chemistry. B · 2022Article
- The Nitrogen Atom of Vitamin BInternational journal of molecular sciences · 2022Article
- Determinants for α4β2 vs. α3β4 Subtype Selectivity of Pyrrolidine-Based nAChRs Ligands: A Computational Perspective with Focus on Recent cryo-EM Receptor Structures.Molecules (Basel, Switzerland) · 2021Article
- Computational approach towards the design of artemisinin-thymoquinone hybrids against main protease of SARS-COV-2.Future journal of pharmaceutical sciences · 2021Article
- A Methyl Scan of the Pyrrolidinium Ring of Nicotine Reveals Significant Differences in Its Interactions withMolecular pharmacology · 2020Article
- Progress in nicotinic receptor structural biology.Neuropharmacology · 2020Review
- A Functional Comparison of Homopentameric Nicotinic Acetylcholine Receptors (ACR-16) Receptors FromFrontiers in molecular neuroscience · 2020Article
- Methylpiperidinium Iodides as Novel Antagonists for α7 Nicotinic Acetylcholine Receptors.Frontiers in pharmacology · 2018Article
- Probing for and Quantifying Agonist Hydrogen Bonds in α6β2 Nicotinic Acetylcholine Receptors.Biochemistry · 2017Article
- (S)-5-ethynyl-anabasine, a novel compound, is a more potent agonist than other nicotine alkaloids on the nematode Asu-ACR-16 receptor.International journal for parasitology. Drugs and drug resistance · 2017Article
- Organocatalyzed, Photoredox Heteroarylation of 2-Trifluoroboratochromanones via C-H Functionalization.Organic letters · 2017Article
- Molecular recognition at cholinergic synapses: acetylcholine versus choline.The Journal of physiology · 2017Article
- AutoDock-GIST: Incorporating Thermodynamics of Active-Site Water into Scoring Function for Accurate Protein-Ligand Docking.Molecules (Basel, Switzerland) · 2016Article
Corrections and comments
- Commented on by
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Pharmacophore models for nicotinic agonists have been proposed for four decades. Central to these models is the presence of a cationic nitrogen and a hydrogen bond acceptor. It is now well-established that the cationic center makes an important cation-pi interaction to a conserved tryptophan, but the donor to the proposed hydrogen bond acceptor has been more challenging to identify. A structure of nicotine bound to the acetylcholine binding protein predicted that the binding partner of the pharmacophore's second component was a water molecule, which also hydrogen bonds to the backbone of the complementary subunit of the receptors. Here we use unnatural amino acid mutagenesis coupled with agonist analogs to examine whether such a hydrogen bond is functionally significant in the alpha4beta2 neuronal nAChR, the receptor most associated with nicotine addiction. We find evidence for the hydrogen bond with the agonists nicotine, acetylcholine, carbamylcholine, and epibatidine. These data represent a completed nicotinic pharmacophore and offer insight into the design of new therapeutic agents that selectively target these receptors.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.