title: 2'-(R)-Fluorinated mC, hmC, fC and caC triphosphates are substrates for DNA polymerases and TET-enzymes.
abstract: A deeper investigation of the chemistry that occurs on the newly discovered epigenetic DNA bases 5-hydroxymethyl-(hmdC), 5-formyl-(fdC), and 5-carboxy-deoxycytidine (cadC) requires chemical tool compounds, which are able to dissect the different potential reaction pathways in cells. Here we report that the 2'-(R)-fluorinated derivatives F-hmdC, F-fdC, and F-cadC, which are resistant to removal by base excision repair, are good substrates for DNA polymerases and TET enzymes. This result shows that the fluorinated compounds are ideal tool substances to investigate potential C-C-bond cleaving reactions in the context of active demethylation.
authors.affiliation: Center for Integrated Protein Science, Department of Chemistry, Ludwig-Maximilians-Universität München, Butenandtstraße 5-13, 81377 Munich, Germany. Thomas.carell@lmu.de.
authors.forename: A S
authors.initials: AS
authors.lastname: Schröder
authors.affiliation: Center for Integrated Protein Science, Department of Chemistry, Ludwig-Maximilians-Universität München, Butenandtstraße 5-13, 81377 Munich, Germany. Thomas.carell@lmu.de.
authors.forename: E
authors.initials: E
authors.lastname: Parsa
authors.affiliation: Center for Integrated Protein Science, Department of Chemistry, Ludwig-Maximilians-Universität München, Butenandtstraße 5-13, 81377 Munich, Germany. Thomas.carell@lmu.de.
authors.forename: K
authors.initials: K
authors.lastname: Iwan
authors.affiliation: Center for Integrated Protein Science, Department of Chemistry, Ludwig-Maximilians-Universität München, Butenandtstraße 5-13, 81377 Munich, Germany. Thomas.carell@lmu.de.
authors.forename: F R
authors.initials: FR
authors.lastname: Traube
authors.affiliation: Center for Integrated Protein Science, Department of Chemistry, Ludwig-Maximilians-Universität München, Butenandtstraße 5-13, 81377 Munich, Germany. Thomas.carell@lmu.de.
authors.forename: M
authors.identifier: http://orcid.org/0000-0003-4342-3831
authors.initials: M
authors.lastname: Wallner
authors.affiliation: Center for Integrated Protein Science, Department of Chemistry, Ludwig-Maximilians-Universität München, Butenandtstraße 5-13, 81377 Munich, Germany. Thomas.carell@lmu.de.
authors.forename: S
authors.initials: S
authors.lastname: Serdjukow
authors.affiliation: Center for Integrated Protein Science, Department of Chemistry, Ludwig-Maximilians-Universität München, Butenandtstraße 5-13, 81377 Munich, Germany. Thomas.carell@lmu.de.
authors.forename: T
authors.identifier: http://orcid.org/0000-0001-7898-2831
authors.initials: T
authors.lastname: Carell
mesh_terms: D003562:Cytidine / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D049308:Dioxygenases / Q000378:metabolism*; D044127:Epigenesis, Genetic; D057809:HEK293 Cells; D054879:Halogenation; D006801:Humans; D011122:Polyphosphates / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D011122:Polyphosphates; D003562:Cytidine; D004247:DNA; D049308:Dioxygenases; D004259:DNA-Directed DNA Polymerase; C005692:triphosphoric acid