ArticleACS chemical neuroscience2015
Role for the propofol hydroxyl in anesthetic protein target molecular recognition.
Article in ACS chemical neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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.
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- Biophysical insights into a cryptic ligand site in the hydrophobic core of human PCNA.Biophysical journal · 2026Article
- Functionalization of 1,3-Diisopropylbenzene to Probe the Antagonism of Propofol Anesthesia.ACS chemical neuroscience · 2025Article
- Current and Developing Approaches for Facilitating Emergence from General Anesthesia.Anesthesiology · 2025Review
- Antagonism of propofol anesthesia by alkyl-fluorobenzene derivatives.Scientific reports · 2024Article
- Time to Wake Up! The Ongoing Search for General Anesthetic Reversal Agents.Anesthesiology · 2024Article
- Antagonism of Propofol Anesthesia by Alkyl-fluorobenzene Derivatives.Research square · 2024Article
- A homogeneous time-resolved fluorescence screen to identify SIRT2 deacetylase and defatty-acylase inhibitors.PloS one · 2024Article
- Binding Sites and the Mechanism of Action of Propofol and a Photoreactive Analogue in Prokaryotic Voltage-Gated Sodium Channels.ACS chemical neuroscience · 2021Article
- Mechanistic basis of propofol-induced disruption of kinesin processivity.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Synthesis and Characterization of a Diazirine-Based Photolabel of the Nonanesthetic Fropofol.ACS chemical neuroscience · 2021Article
- Substrate-Dependent Modulation of SIRT2 by a Fluorescent Probe, 1-Aminoanthracene.Biochemistry · 2020Article
- The actin 'A-triad's' role in contractile regulation in health and disease.The Journal of physiology · 2020Review
- The role of propofol hydroxyl group in 5-lipoxygenase recognition.Biochemical and biophysical research communications · 2020Article
- Fropofol prevents disease progression in mice with hypertrophic cardiomyopathy.Cardiovascular research · 2020Article
- Towards a Comprehensive Understanding of Anesthetic Mechanisms of Action: A Decade of Discovery.Trends in pharmacological sciences · 2019Review
- Alkylphenol inverse agonists of HCN1 gating: H-bond propensity, ring saturation and adduct geometry differentially determine efficacy and potency.Biochemical pharmacology · 2019Article
- Propofol inhibits prokaryotic voltage-gated NaThe Journal of general physiology · 2018Article
- Propofol inhibits the voltage-gated sodium channel NaChBac at multiple sites.The Journal of general physiology · 2018Article
- Identification of binding sites contributing to volatile anesthetic effects on GABA type A receptors.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Fropofol decreases force development in cardiac muscle.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Propofol is a widely used intravenous general anesthetic. We synthesized 2-fluoro-1,3-diisopropylbenzene, a compound that we call "fropofol", to directly assess the significance of the propofol 1-hydroxyl for pharmacologically relevant molecular recognition in vitro and for anesthetic efficacy in vivo. Compared to propofol, fropofol had a similar molecular volume and only a small increase in hydrophobicity. Isothermal titration calorimetry and competition assays revealed that fropofol had higher affinity for a protein site governed largely by van der Waals interactions. Within another protein model containing hydrogen bond interactions, propofol demonstrated higher affinity. In vivo, fropofol demonstrated no anesthetic efficacy, but at high concentrations produced excitatory activity in tadpoles and mice; fropofol also antagonized propofol-induced hypnosis. In a propofol protein target that contributes to hypnosis, α1β2γ2L GABAA receptors, fropofol demonstrated no significant effect alone or on propofol positive allosteric modulation of the ion channel, suggesting an additional requirement for the 1-hydroxyl within synaptic GABAA receptor site(s). However, fropofol caused similar adverse cardiovascular effects as propofol by a dose-dependent depression of myocardial contractility. Our results directly implicate the propofol 1-hydroxyl as contributing to molecular recognition within protein targets leading to hypnosis, but not necessarily within protein targets leading to side effects of the drug.
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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.