Highly Efficient Fluorescent Interstrand Photo‐crosslinking of DNA Duplexes Labeled with 5‐Fluoro‐4‐thio‐2′‐<i>O</i>‐methyluridine

Nowak-Karnowska, Joanna; Chebib, Ziad; Milecki, Jan; Franzen, Stefan; Skalski, Bohdan

doi:10.1002/cbic.201402182

Cited by 7 publications

(13 citation statements)

References 27 publications

(10 reference statements)

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“…70 In two dsDNA sequences labeled with 5-BrdU, a photoinduced inter-CL was observed only in the sequence containing a bulge in the labeled region. Furthermore, Skalski's group 88 observed an inter-CL lesion in dsDNA comprising a d(A FS UA) motif (where FS U stands for 5-fluoro-4-thio-2′-O-methyluridine), while Fujimoto et al 89 reported a novel interstrand photo-cross-linked product in oligonucleotides containing the p-carbamoylvinyl phenol derivative of nucleoside. Undoubtedly, the interstrand cross-link formation in DNA appeals to a number of research groups, since this kind of damage belongs to the most cytotoxic ones and control over it cannot be overestimated as far as anticancer therapy is concerned.…”

Section: Uv-induced Damage To Dna Labeled Withmentioning

confidence: 99%

Mechanisms of Damage to DNA Labeled with Electrophilic Nucleobases Induced by Ionizing or UV Radiation

et al. 2015

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Hypoxia--a hallmark of solid tumors--makes hypoxic cells radioresistant. On the other hand, DNA, the main target of anticancer therapy, is not sensitive to the near UV photons and hydrated electrons, one of the major products of water radiolysis under hypoxic conditions. A possible way to overcome these obstacles to the efficient radio- and photodynamic therapy of cancer is to sensitize the cellular DNA to electrons and/or ultraviolet radiation. While incorporated into genomic DNA, modified nucleosides, 5-bromo-2'-deoxyuridine in particular, sensitize cells to both near-ultraviolet photons and γ rays. It is believed that, in both sensitization modes, the reactive nucleobase radical is formed as a primary product which swiftly stabilizes, leading to serious DNA damage, like strand breaks or cross-links. However, despite the apparent similarity, such radio- and photosensitization of DNA seems to be ruled by fundamentally different mechanisms. In this review, we demonstrate that the most important factors deciding on radiodamage to the labeled DNA are (i) the electron affinity (EA) of modified nucleoside (mNZ), (ii) the local surroundings of the label that significantly influences the EA of mNZ, and (iii) the strength of the chemical bond holding together the substituent and a nucleobase. On the other hand, we show that the UV damage to sensitized DNA is governed by long-range photoinduced electron transfer, the efficiency of which is controlled by local DNA sequences. A critical review of the literature mechanisms concerning both types of damage to the labeled biopolymer is presented. Ultimately, the perspectives of studies on DNA sensitization in the context of cancer therapy are discussed.

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Section: Uv-induced Damage To Dna Labeled Withmentioning

confidence: 99%

Mechanisms of Damage to DNA Labeled with Electrophilic Nucleobases Induced by Ionizing or UV Radiation

et al. 2015

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“…Thionucleotides, especially 4-thiouridine (s4U) and 6-thioguanosine (s6G), are photosensitive molecules that photocrosslink to both proteins and nucleic acids, and this feature is a major reason for their application in various investigations 3–10 . In the context of duplex RNA, it has been shown that 4-thiouridine efficiently crosslinks to nucleotides in the opposite strand 7 . Photophysics and photochemistry of these crosslinking processes on the level of nucleosides and oligonucleotides is very well documented 6,9 .…”

Section: Introductionmentioning

confidence: 99%

Thermodynamic and structural contributions of the 6-thioguanosine residue to helical properties of RNA

Gładysz

Andrałojć

Czapik

et al. 2019

Sci Rep

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Thionucleotides, especially 4-thiouridine and 6-thioguanosine, are photosensitive molecules that photocrosslink to both proteins and nucleic acids, and this feature is a major reason for their application in various investigations. To get insight into the thermodynamic and structural contributions of 6-thioguanosine to the properties of RNA duplexes a systematic study was performed. In a series of RNA duplexes, selected guanosine residues located in G-C base pairs, mismatches (G-G, G-U, and G-A), or 5′ and 3′-dangling ends were replaced with 6-thioguanosine. Generally, the presence of 6-thioguanosine diminishes the thermodynamic stability of RNA duplexes. This effect depends on its position within duplexes and the sequence of adjacent base pairs. However, when placed at a dangling end a 6-thioguanosine residue actually exerts a weak stabilizing effect. Furthermore, the structural effect of 6-thioguanosine substitution appears to be minimal based on NMR and Circular Dichroism (CD) data.

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“…Selective photomodulation of DNA has been considered as an alternative approach to control gene expression in a timely and persistent manner. In recent years, several elegant studies have shown that interstrand photo-cross-linking (ICL) of a designed oligomer targeting a complementary DNA strand is achievable by photolysis in the UV region. − Other approaches to DNA photomodulation include the activation of a furanyl modified oligomer by an external photosensitizer (PS) and by ruthenium-tethered oligomers that are photoactivated by visible light (442 nm) …”

Section: Introductionmentioning

confidence: 99%

PNA–Rose Bengal Conjugates as Efficient DNA Photomodulators

Shemesh

Yavin

2015

Bioconjugate Chem.

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Selective photoinduced modulation of DNA may provide a powerful therapeutic tool allowing spatial and temporal control of the photochemical reaction. We have explored the photoreactivity of peptide nucleic acid (PNA) conjugates that were conjugated to a highly potent photosensitizer, Rose Bengal (RB). In addition, a short PEGylated peptide (K-PEG8-K) was conjugated to the C-terminus of the PNA to improve its water solubility. A short irradiation (visible light) of PNA conjugates with a synthetic DNA resulted in highly efficient photomodulation of the DNA as evidenced by polyacrylamide gel electrophoresis (PAGE). In addition, a PNA-RB conjugate replacing K-PEG8-K with four l-glutamic acids (E4) was found to be photoinactive. Irradiation of active PNA-RB conjugates with synthetic DNA in D20 augments the photoactivity; supporting the involvement of singlet oxygen. PAGE, HPLC, and MALDI-TOF analyses indicate that PNA-DNA photo-cross-linking is a significant pathway in the observed photoreactivity. Selective photo-cross-linking of such PNA-RB conjugates may be a novel approach to selective photodynamic therapy (sPDT) as such molecules would be sequence-specific, cell-permeable, and photoactivated in the visible region.

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Highly Efficient Fluorescent Interstrand Photo‐crosslinking of DNA Duplexes Labeled with 5‐Fluoro‐4‐thio‐2′‐O‐methyluridine

Cited by 7 publications

References 27 publications

Mechanisms of Damage to DNA Labeled with Electrophilic Nucleobases Induced by Ionizing or UV Radiation

Mechanisms of Damage to DNA Labeled with Electrophilic Nucleobases Induced by Ionizing or UV Radiation

Thermodynamic and structural contributions of the 6-thioguanosine residue to helical properties of RNA

PNA–Rose Bengal Conjugates as Efficient DNA Photomodulators

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