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- W2895562191 abstract "Abstract Cyclic nucleotide-gated (CNG) and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are tetrameric non-specific cation channels in the plasma membrane that are activated by either cAMP or cGMP binding to specific binding domains incorporated in each subunit. Typical apparent affinities of these channels for these cyclic nucleotides range from several hundred nanomolar to tens of micromolar. Here we synthesized and characterized novel cAMP and cGMP derivatives by substituting either hydrophobic alkyl chains or similar-sized more hydrophilic heteroalkyl chains to the 8-position of the purine ring with the aim to obtain full agonists of higher potency. The compounds were tested in homotetrameric CNGA2, heterotetrameric CNGA2:CNGA4:CNGB1b and homotetrameric HCN2 channels. We show that nearly all compounds are full agonists and that longer alkyl chains systematically increase the apparent affinity, at the best more than 30 times. The effects are stronger in CNG than HCN2 channels which, however, are constitutively more sensitive to cAMP. Kinetic analyses reveal that the off-rate is significantly slowed by the hydrophobic alkyl chains. Molecular dynamics simulations and free energy calculations suggest that an intricate enthalpy - entropy compensation underlies the higher apparent affinity of the derivatives with the longer alkyl chains, which is shown to result from a reduced loss of configurational entropy upon binding." @default.
- W2895562191 created "2018-10-12" @default.
- W2895562191 creator A5013747364 @default.
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- W2895562191 date "2018-10-08" @default.
- W2895562191 modified "2023-10-17" @default.
- W2895562191 title "Hydrophobic alkyl chains substituted to the 8-position of cyclic nucleotides enhance activation of CNG and HCN channels by an intricate enthalpy - entropy compensation" @default.
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- W2895562191 cites W1974273055 @default.
- W2895562191 cites W1976965902 @default.
- W2895562191 cites W1979411530 @default.
- W2895562191 cites W1979915001 @default.
- W2895562191 cites W1983786684 @default.
- W2895562191 cites W1986611382 @default.
- W2895562191 cites W1988092025 @default.
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- W2895562191 cites W1994962594 @default.
- W2895562191 cites W1995591233 @default.
- W2895562191 cites W2008142951 @default.
- W2895562191 cites W2010973571 @default.
- W2895562191 cites W2012632454 @default.
- W2895562191 cites W2013311592 @default.
- W2895562191 cites W2013413259 @default.
- W2895562191 cites W2014660839 @default.
- W2895562191 cites W2015433868 @default.
- W2895562191 cites W2016688851 @default.
- W2895562191 cites W2020400571 @default.
- W2895562191 cites W2021155141 @default.
- W2895562191 cites W2021451097 @default.
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- W2895562191 cites W2034105640 @default.
- W2895562191 cites W2034176125 @default.
- W2895562191 cites W2057646733 @default.
- W2895562191 cites W2058004635 @default.
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- W2895562191 cites W2075957044 @default.
- W2895562191 cites W2085241378 @default.
- W2895562191 cites W2087823674 @default.
- W2895562191 cites W2099091048 @default.
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- W2895562191 cites W2102377211 @default.
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- W2895562191 cites W2167344126 @default.
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- W2895562191 cites W2301068131 @default.
- W2895562191 cites W2340389505 @default.
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- W2895562191 doi "https://doi.org/10.1038/s41598-018-33050-5" @default.
- W2895562191 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6175941" @default.
- W2895562191 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30297855" @default.
- W2895562191 hasPublicationYear "2018" @default.
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