Photochemical Generation of Benzyl Cations That Selectively Cross-Link Guanine and Cytosine in DNA

Wang, Yibin; Liu, Shuo; Lin, Zechao; Fan, Yukai; Wang, Yinsheng; Peng, Xiaohua

doi:10.1021/acs.orglett.6b00755

Cited by 15 publications

(42 citation statements)

References 45 publications

(72 reference statements)

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“…Then Li and Greenberg demonstrated that photoirradiation of the modified thymidines generated both 5‐(2′‐dexoyuridinyl)methyl radical and cation, whereas only cation intermediates directly produced DNA ICL products. Recently, Peng and co‐workers found that several bifunctional aromatic boronates cross‐linked DNA through carbocation formation upon 350 nm irradiation –…”

Section: Introductionmentioning

confidence: 99%

“…There are still only a few compounds with limited structure variations that have been reported to induce DNA cross‐linking through the carbocation pathway upon photoirradiation. All of the existing bifunctional compounds capable of efficiently cross‐linking DNA via photogenerated carbocations contain boronate ester groups (e.g., 1 a’ and 1 b’ ) . However, in species such as 1 a’ and 1 b’ the carbocations are generated by dissociation of the leaving groups L, and the role of the boronate ester functionality appears to be as a modulator of the cationic intermediates.…”

Section: Introductionmentioning

confidence: 99%

“…However, in species such as 1 a’ and 1 b’ the carbocations are generated by dissociation of the leaving groups L, and the role of the boronate ester functionality appears to be as a modulator of the cationic intermediates. We wanted to know how general the cross‐linking property of species such as 1 a’ and 1 b’ is, and whether substituents other than boronate esters might make the photoinitiated cross‐linking reaction more efficient (compounds 1 a’ and 1 b’ required more than eight hours to complete the cross‐linking reaction).…”

Section: Introductionmentioning

confidence: 99%

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Substituents Have a Large Effect on Photochemical Generation of Benzyl Cations and DNA Cross‐Linking

Fan

Sun

Peng

2018

Chemistry A European J

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Photoactivated DNA interstrand cross-linking agents have a wide range of biological applications. Recently, several aryl boronates have been reported to induce DNA interstrand cross-link (ICL) formation via carbocations upon photoirradiation. Herein, we synthesized a series of new bifunctional phenyl compounds to test the generality of such a mechanism, and to understand how the chemical structure influences carbocation formation and the DNA cross-linking process. These compounds efficiently form DNA ICLs via generated benzyl cations upon 350 nm irradiation. The DNA cross-linking efficiency and the pathway for carbocation generation depend on both the aromatic substituents and the leaving groups. Bromine as a leaving group facilitates the DNA cross-linking process in comparison with trimethyl ammonium salt. Both electron-donating and -withdrawing substituents induce bathochromic shifts, which favor photoinduced DNA ICL formation. For the bromides, the benzyl cation intermediates were generated through oxidation of the corresponding benzyl radicals. However, for the ammonia salts, the benzyl cations were formed through two pathways: either through oxidation of the benzyl radicals or by direct heterolysis of the C-N bond. Photoinduced C-N homolysis to form benzyl radicals occurred with compounds having donating substituents, whereas direct heterolysis of the C-N bond occurred with those bearing withdrawing substituents. The adducts formed between 1 a and four natural nucleosides were characterized, indicating that the alkylation sites for the photogenerated benzyl cations are dG, dA, and dC.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Substituents Have a Large Effect on Photochemical Generation of Benzyl Cations and DNA Cross‐Linking

Fan

Sun

Peng

2018

Chemistry A European J

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“…Based on our previous work,[41] compounds 2a–5a with Br as a leaving group were synthesized via borylation of the corresponding 1-bromobenzene 6, 10, 13 , or 16 using n-butyllithium and isopropoxyboronic acid pinacol ester followed by bromination with N -bromosuccinimide (NBS) and azobisisobutyronitrile (AIBN) (Note: To be consistent, the numbering shown for 1a and 1b is used for all compounds described in this paper). Compound 6 is commercially available, while 10, 13 , and 16 were synthesized starting from methoxy substituted benzenes 8, 12 , and 15 .…”

Section: Resultsmentioning

confidence: 99%

Hydrogen peroxide activated quinone methide precursors with enhanced DNA cross-linking capability and cytotoxicity towards cancer cells

Wang

Fan

Balakrishnan

et al. 2017

European Journal of Medicinal Chemistry

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Quinone methide (QM) formation induced by endogenously generated H2O2 is attractive for biological and biomedical applications. To overcome current limitations due to low biological activity of H2O2-activated QM precursors, we are introducing herein several new arylboronates with electron donating substituents at different positions of benzene ring and/or different neutral leaving groups. The reaction rate of the arylboronate esters with H2O2 and subsequent bisquinone methides formation and DNA cross-linking was accelerated with the application of Br as a leaving group instead of acetoxy groups. Additionally, a donating group placed meta to the nascent exo-methylene group of the quinone methide greatly improves H2O2-induced DNA interstrand cross-link formation as well as enhances the cellular activity. Multiple donating groups decrease the stability and DNA cross-linking capability, which lead to low cellular activity. A cell-based screen demonstrated that compounds 2a and 5a with a OMe or OH group dramatically inhibited the growth of various tissue-derived cancer cells while normal cells were less affected. Induction of H2AX phosphorylation by these compounds in CLL lymphocytes provide evidence for a correlation between cell death and DNA damage. The compounds presented herein showed potent anticancer activities and selectivity, which represent a novel scaffold for anticancer drug development.

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“…or modified bases with possibilities for cross-linking(Stephenson et al 2011;Wang et al 2016; Zhang and Paukstelis 2016) etc.). On a recent paper, Tomàs Gamasa et al(Tomas- Gamasa et al 2015) have reported formation of selective, reversible and highly thermostable DNA interstrand cross-links based on the reversible imine chemistry concept.…”

mentioning

confidence: 99%

Multimodal plasmonic biosensing nanostructures prepared by DNA-directed immobilization of multifunctional DNA-gold nanoparticles

Tort

Salvador

Marco

2017

Biosensors and Bioelectronics

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Biofunctional multimodal plasmonic nanostructures suitable for multiplexed localized surface plasmon resonance (LSPR) biosensing have been created by DNA-directed immobilization (DDI) of two distinct multifunctional biohybrid gold nanoparticles. Gold nanoparticles (AuNP) of distinct sizes, and therefore showing distinct plasmon resonant peaks (RP), have been biofunctionalized and codified with two different single stranded-DNA (ssDNA) chains. One of these oligonucleotide chains has been specifically designed to direct each AuNP to a distinct location of the surface of a DNA microarray chip through specific hybridization with complementary oligonucleotide strands. Scanning Electron Microscopy (SEM) has been used to demonstrate selective immobilization of each AuNP on distinct spots. The second ssDNA chain of the AuNPs provides the possibility to introduce by hybridization distinct types of bioactive molecules or bioreceptors, on a reversible manner. In this work, hapten-oligonucleotide bioconjugate probes, with sequences complementary to the second ssDNA linked to the AuNP, have been synthesized and used to create multiplexed hapten-biofuncionalized plasmonic nanostructures. The oligonucleotide probes consist on anabolic androgenic steroid haptens (AAS) covalently linked to specifically designed oligonucleotide sequences. The biofunctionality of these plasmonic nanostructures has been demonstrated by fluorescent microarray immunoassay and LSPR measurements, recording the shift of the RP produced after the antibody binding to the corresponding hapten-oligonucleotide probes immobilized on the nanostructured surface. Preliminary data show that this approach could allow manufacturing multifunctional multimodal LSPR chips for multiplexed analysis of different substances reaching very good detectability. Thus, small molecular weigh, analytes such as stanozolol (ST,) could be detected at concentrations in the low nM range. The results here presented open the door for an easy way to construct site-encoded multiplexed multimodal LSPR sensor transducers, combining the DDI strategies with multimodal biohybrid nanoparticles showing distinct optical properties.

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Photochemical Generation of Benzyl Cations That Selectively Cross-Link Guanine and Cytosine in DNA

Cited by 15 publications

References 45 publications

Substituents Have a Large Effect on Photochemical Generation of Benzyl Cations and DNA Cross‐Linking

Substituents Have a Large Effect on Photochemical Generation of Benzyl Cations and DNA Cross‐Linking

Hydrogen peroxide activated quinone methide precursors with enhanced DNA cross-linking capability and cytotoxicity towards cancer cells

Multimodal plasmonic biosensing nanostructures prepared by DNA-directed immobilization of multifunctional DNA-gold nanoparticles

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