title: Light-induced oxidation of the telomeric G4 DNA in complex with Zn(II) tetracarboxymethyl porphyrin.
abstract: Structure-specific ligands are convenient tools for the recognition, targeting or probing of non-canonical DNA structures. Porphyrin derivatives exhibit a preference for interaction with G-quadruplex (G4) structures over canonical duplex DNA and are able to cause photoinducible damage to nucleic acids. Here, we show that Zn(II) 5,10,15,20-tetrakis(N-carboxymethyl-4-pyridinium)porphyrin ( ZNP1: ) interacts with different conformations of the telomeric sequence d(TAGGG(TTAGGG)3) at submicromolar concentrations without any detectible disturbance of the particular fold. Among different folds, potassium (3+1) hybrid G4-structure. reveal the highest affinity to ZNP1: The pattern of guanine oxidation is specific for each telomeric DNA conformation and may serve as an additional tool for probing the G4 topology. The potassium (3+1) and parallel G4 conformations are more susceptible to light-induced oxidation than the sodium G4 conformation or double helix of the telomeric DNA. The major products of the guanine modifications are spiroiminodihydantoin (Sp) and 8-oxoguanine (8-oxoG). ZNP1: -induced oxidation of guanines results in the structural rearrangement of parallel and (3+1) G4 conformations yielding an antiparallel-like G4 conformation. The mechanism of the observed light-induced conformational changes is discussed.
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov str., 32, 119991 Moscow, Russia abeniaminov@mail.ru.
authors.forename: Artemy D
authors.initials: AD
authors.lastname: Beniaminov
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov str., 32, 119991 Moscow, Russia.
authors.forename: Roman A
authors.initials: RA
authors.lastname: Novikov
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov str., 32, 119991 Moscow, Russia.
authors.forename: Olga K
authors.initials: OK
authors.lastname: Mamaeva
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov str., 32, 119991 Moscow, Russia.
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Mitkevich
authors.affiliation: Institute for Physical-Chemical Medicine of Ministry of Public Health, Malaya Pirogovskaya str. 1a, 119435 Moscow, Russia.
authors.forename: Igor P
authors.initials: IP
authors.lastname: Smirnov
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov str., 32, 119991 Moscow, Russia.
authors.forename: Mikhail A
authors.initials: MA
authors.lastname: Livshits
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov str., 32, 119991 Moscow, Russia.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Shchyolkina
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov str., 32, 119991 Moscow, Russia uzhny@mail.ru.
authors.forename: Dmitry N
authors.initials: DN
authors.lastname: Kaluzhny
mesh_terms: D001665:Binding Sites; D002151:Calorimetry / Q000379:methods; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry; D054856:G-Quadruplexes; D006147:Guanine / Q000031:analogs & derivatives / Q000737:chemistry; D006151:Guanosine / Q000031:analogs & derivatives / Q000737:chemistry; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D009690:Nucleic Acid Conformation; D010084:Oxidation-Reduction; D011166:Porphyrins / Q000737:chemistry*; D011188:Potassium / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D013141:Spiro Compounds / Q000737:chemistry; D016615:Telomere / Q000235:genetics; D015032:Zinc / Q000737:chemistry*
chemical_list: D011166:Porphyrins; D013141:Spiro Compounds; C408822:spiroiminodihydantoin; D006151:Guanosine; C024829:8-hydroxyguanine; D006147:Guanine; D004247:DNA; D015032:Zinc; D011188:Potassium