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@ARTICLE{Otte:863298,
      author       = {Otte, Maik and Schweinitz, Andrea and Lelle, Marco and
                      Thon, Susanne and Enke, Uta and Yüksel, Sezin and
                      Schmauder, Ralf and Bonus, Michele and Gohlke, Holger and
                      Benndorf, Klaus},
      title        = {{N}ovel {F}luorescent {C}yclic {N}ucleotide {D}erivatives
                      to {S}tudy {CNG} and {HCN} {C}hannel {F}unction},
      journal      = {Biophysical journal},
      volume       = {116},
      number       = {12},
      issn         = {0006-3495},
      address      = {Bethesda, Md.},
      publisher    = {Soc.},
      reportid     = {FZJ-2019-03385},
      pages        = {2411-2422},
      year         = {2019},
      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.},
      cin          = {JSC / NIC / ICS-6},
      ddc          = {570},
      cid          = {I:(DE-Juel1)JSC-20090406 / I:(DE-Juel1)NIC-20090406 /
                      I:(DE-Juel1)ICS-6-20110106},
      pnm          = {511 - Computational Science and Mathematical Methods
                      (POF3-511) / Forschergruppe Gohlke $(hkf7_20170501)$},
      pid          = {G:(DE-HGF)POF3-511 / $G:(DE-Juel1)hkf7_20170501$},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31130235},
      UT           = {WOS:000471862300019},
      doi          = {10.1016/j.bpj.2019.05.006},
      url          = {https://juser.fz-juelich.de/record/863298},
}