ArticleBiophysical journal2019
Novel Fluorescent Cyclic Nucleotide Derivatives to Study CNG and HCN Channel Function.
Article in Biophysical journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Anisotropic Network Analysis of Open/Closed HCN4 Channel Advocates Asymmetric Subunit Cooperativity in cAMP Modulation of Gating.Journal of chemical information and modeling · 2024Article
- cAMP binding to closed pacemaker ion channels is cooperative.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A high affinity switch for cAMP in the HCN pacemaker channels.Nature communications · 2024Article
- Fast functional mapping of ligand-gated ion channels.Communications biology · 2023Article
- Enlightening activation gating in P2X receptors.Purinergic signalling · 2022Review
- Functional and structural characterization of interactions between opposite subunits in HCN pacemaker channels.Communications biology · 2022Article
- Uncoupling of Voltage- and Ligand-Induced Activation in HCN2 Channels by Glycine Inserts.Frontiers in physiology · 2022Article
- Single-molecule imaging with cell-derived nanovesicles reveals early binding dynamics at a cyclic nucleotide-gated ion channel.Nature communications · 2021Article
- Allosteric signaling in C-linker and cyclic nucleotide-binding domain of HCN2 channels.Biophysical journal · 2021Article
- Fluorophore-Labeled Cyclic Nucleotides as Potent Agonists of Cyclic Nucleotide-Regulated Ion Channels.Chembiochem : a European journal of chemical biology · 2020Article
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10 authors.
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Abstract
A highly specific molecular interaction of diffusible ligands with their receptors belongs to the key processes in cellular signaling. Because an appropriate method to monitor the unitary binding events is still missing, most of our present knowledge is based on ensemble signals recorded from a big number of receptors, such as ion currents or fluorescence changes of suitably labeled receptors, and reasoning from these data to the ligand binding. To study the binding process itself, appropriately tagged ligands are required that fully activate the receptors and report the binding at the same time. Herein, we tailored a series of 18 novel fluorescent cyclic nucleotide derivatives by attaching 6 different dyes via different alkyl linkers to the 8-position of the purine ring of cGMP or cAMP. The biological activity was determined in inside-out macropatches containing either homotetrameric (CNGA2), heterotetrameric (CNGA2:CNGA4:CNGB1b), or hyperpolarization-activated cyclic nucleotide-modulated (HCN2) channels. All these novel fluorescent ligands are efficient to activate the channels, and the potency of most of them significantly exceeded that of the natural cyclic nucleotides cGMP or cAMP. Moreover, some of them showed an enhanced brightness when bound to the channels. The best of our derivatives bear great potential to systematically analyze the activation mechanism in CNG and HCN channels, at both the level of ensemble and single-molecule analyses.
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