Chemical Synthesis of Cross-Link Lesions Found in Nitrous Acid Treated DNA:  A General Method for the Preparation of N2-Substituted 2‘-Deoxyguanosines

Harwood, Eric A.; Hopkins, Paul B.; Sigurdsson, Snorri Th.

doi:10.1021/jo991501+

Cited by 65 publications

(50 citation statements)

References 29 publications

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“…Pitts et al, 1978) or interhelical DNA cross-links (e.g. Harwood et al, 2000). Different formation pathways in the atmosphere were proposed during the last decades (e.g.…”

Section: Introductionmentioning

confidence: 99%

Heterogeneous conversion of NO<sub>2</sub> on secondary organic aerosol surfaces: A possible source of nitrous acid (HONO) in the atmosphere?

2003

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Abstract. The heterogeneous conversion of NO 2 on different secondary organic aerosols (SOA) was investigated with the focus on a possible formation of nitrous acid (HONO). In one set of experiments different organic aerosols were produced in the reactions of O 3 with α-pinene, limonene or catechol and OH radicals with toluene or limonene, respectively. The aerosols were sampled on filters and exposed to humidified NO 2 mixtures under atmospheric conditions. The estimated upper limits for the uptake coefficients of NO 2 and the reactive uptake coefficients NO 2 →HONO are in the range of 10 −6 and 10 −7 , respectively. The integrated HONO formation for 1 h reaction time was < 10 13 cm −2 geometrical surface and < 10 17 g −1 particle mass. In a second set of experiments the conversion of NO 2 into HONO in the presence of organic particles was carried out in an aerosol flow tube under atmospheric conditions. In this case the aerosols were produced in the reaction of O 3 with β-pinene, limonene or catechol, respectively. The upper limits for the reactive uptake coefficients NO 2 →HONO were in the range of 7 × 10 −7 − 9 × 10 −6 . The results from the present study show that heterogeneous formation of nitrous acid on secondary organic aerosols (SOA) is unimportant for the atmosphere.

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“…Pitts et al, 1978) or interhelical DNA cross-links (e.g. Harwood et al, 2000). Different formation pathways in the atmosphere were proposed during the last decades (e.g.…”

Section: Introductionmentioning

confidence: 99%

Heterogeneous conversion of NO<sub>2</sub> on secondary organic aerosol surfaces: A possible source of nitrous acid (HONO) in the atmosphere?

2003

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“…Both of these proteins are involved in the repair of cross-linked DNA (18). Nitrous acid itself may produce crosslinks directly (26,45), but its mutagenicity for nfi mutants outweighs its lethality (41). Therefore, it is unlikely that the lethality of 3-nitrosoindole or its derivatives is due to crosslinks generated by transnitrosation.…”

Section: Discussionmentioning

confidence: 99%

“…N 2 O 3 is a harmful nitrosating agent that reacts with many cellular constituents, including DNA (57). The N nitrosation of the exocyclic amines of the nucleobases in DNA results in mutagenic deamination (46) and cross-linking of strands (26). Nitrosation of ring nitrogens in DNA destabilizes the glycosylic bond, leading to depurination (36).…”

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confidence: 99%

Production of 3-Nitrosoindole Derivatives by Escherichia coli during Anaerobic Growth

Kwon

Weiss

2009

J Bacteriol

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When Escherichia coli K-12 is grown anaerobically in medium containing tryptophan and sodium nitrate, it produces red compounds. The reaction requires functional genes for trytophanase (tnaA), a tryptophan permease (tnaB), and a nitrate reductase (narG), as well as a natural drop in the pH of the culture. Mass spectrometry revealed that the purified chromophores had mass/charge ratios that closely match those for indole red, indoxyl red, and an indole trimer. These compounds are known products of chemical reactions between indole and nitrous acid. They are derived from an initial reaction of 3-nitrosoindole with indole. Apparently, nitrite that is produced from the metabolic reduction of nitrate is converted in the acid medium to nitrous acid, which leads to the nitrosation of the indole that is generated by tryptophanase. An nfi (endonuclease V) mutant and a recA mutant were selectively killed during the period of chromophore production, and a uvrA strain displayed reduced growth. These effects depended on the addition of nitrate to the medium and on tryptophanase activity in the cells. Unexpectedly, the killing of a tnaA ؉ nfi mutant was not accompanied by marked increases in mutation frequencies for several traits tested. The vulnerability of three DNA repair mutants indicates that a nitrosoindole or a derivative of a nitrosoindole produces lethal DNA damage.Under hypoxic conditions, nitrate replaces oxygen as the preferred electron acceptor in Escherichia coli. The nitrate is first reduced to nitrite by periplasmic and cytoplasmic nitrate reductases, and then nitrite is reduced directly to ammonia by nitrite reductases (22). The nitrite, which is an intermediate, is in equilibrium with molecular nitrous acid (HNO 2 ), which can condense with the loss of water to form N 2 O 3 (dinitrogen trioxide, nitrous anhydride). N 2 O 3 is a harmful nitrosating agent that reacts with many cellular constituents, including DNA (57). The N nitrosation of the exocyclic amines of the nucleobases in DNA results in mutagenic deamination (46) and cross-linking of strands (26). Nitrosation of ring nitrogens in DNA destabilizes the glycosylic bond, leading to depurination (36). The nitrosation of secondary amines and amides can turn them into mutagenic alkylating agents (42, 51). The cell is protected from potential damage by high nitrite reductase activity, by a membrane pump that extrudes excessive nitrite, and by the low pK of HNO 2 , which results in an unfavorable equilibrium for its production at neutral pH (22). Nevertheless, nitrosative mutagenesis does occur under these conditions (56). It results mainly from the apparent production of a small amount of nitric oxide as a by-product of cytoplasmic nitrite reductase (12). The nitric oxide is auto-oxidized to N 2 O 3 when the culture is exposed to air (56).For study of nitrosative mutagenesis under hypoxic conditions, E. coli was grown in sealed tubes in a medium containing nitrate as an electron acceptor (56). In this study, we report our observation that some strains forme...

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“…This is usually unacceptable from a preparative perspective. Alternatively, elegant syntheses of structurally-defined cross-linked duplexes have been devised (Balkrishnen et al, 1996; Carrette et al, 2013; Gao and Orgel, 1999; Gruppi et al, 2014; Haque et al, 2014; Harwood et al, 2000; Hentshel et al, 2012; Hong et al, 2006; Manoharan et al, 1999; Mukherjee et al, 2014; Nakatani et al, 2002; Nishimoto et al, 2013; Noll et al, 2001; O'Flaherty et al, 2013; Pujari et al, 2014; Schärer, 2005; Tomás-Gamasa et al, 2014; Ye et al, 2013), but many of these multi-step organic reaction sequences may not be practical in many of the biochemical and materials science laboratories with interests in cross-linked DNA. In the work described here, we sought a simple, benchtop procedure for the synthesis of DNA duplexes containing a site-specific interstrand cross-link that employs inexpensive commercially available enzymes, chemicals, and oligodeoxynucleotides.…”

Section: Commentarymentioning

confidence: 99%

Simple, High‐Yield Syntheses of DNA Duplexes Containing Interstrand DNA‐DNA Cross‐Links Between an N⁴‐Aminocytidine Residue and an Abasic Site

Varela

Gates

2016

CP Nucleic Acid Chemistry

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The protocol describes the preparation and purification of interstrand DNA-DNA cross-links derived from the reaction of an N4-aminocytidine residue with an abasic site in duplex DNA. The procedures employ inexpensive, commercially-available chemicals and enzymes to carry out post-synthetic modification of commercially-available oligodeoxynucleotides. The yield of cross-linked duplex is typically better than 90%. If purification is required, the cross-linked duplex can be readily separated from single-stranded DNA starting materials by denaturing gel electrophoresis. The resulting covalent hydrazone-based cross-links are stable under physiologically-relevant conditions and may be useful for biophysical studies, structural analyses, DNA repair studies, and materials science applications.

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Chemical Synthesis of Cross-Link Lesions Found in Nitrous Acid Treated DNA: A General Method for the Preparation of N2-Substituted 2‘-Deoxyguanosines

Cited by 65 publications

References 29 publications

Heterogeneous conversion of NO<sub>2</sub> on secondary organic aerosol surfaces: A possible source of nitrous acid (HONO) in the atmosphere?

Heterogeneous conversion of NO<sub>2</sub> on secondary organic aerosol surfaces: A possible source of nitrous acid (HONO) in the atmosphere?

Production of 3-Nitrosoindole Derivatives by Escherichia coli during Anaerobic Growth

Simple, High‐Yield Syntheses of DNA Duplexes Containing Interstrand DNA‐DNA Cross‐Links Between an N⁴‐Aminocytidine Residue and an Abasic Site

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Chemical Synthesis of Cross-Link Lesions Found in Nitrous Acid Treated DNA: A General Method for the Preparation of N2-Substituted 2‘-Deoxyguanosines

Cited by 65 publications

References 29 publications

Heterogeneous conversion of NO&lt;sub&gt;2&lt;/sub&gt; on secondary organic aerosol surfaces: A possible source of nitrous acid (HONO) in the atmosphere?

Heterogeneous conversion of NO&lt;sub&gt;2&lt;/sub&gt; on secondary organic aerosol surfaces: A possible source of nitrous acid (HONO) in the atmosphere?

Production of 3-Nitrosoindole Derivatives by Escherichia coli during Anaerobic Growth

Simple, High‐Yield Syntheses of DNA Duplexes Containing Interstrand DNA‐DNA Cross‐Links Between an N4‐Aminocytidine Residue and an Abasic Site

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Heterogeneous conversion of NO<sub>2</sub> on secondary organic aerosol surfaces: A possible source of nitrous acid (HONO) in the atmosphere?

Heterogeneous conversion of NO<sub>2</sub> on secondary organic aerosol surfaces: A possible source of nitrous acid (HONO) in the atmosphere?

Simple, High‐Yield Syntheses of DNA Duplexes Containing Interstrand DNA‐DNA Cross‐Links Between an N⁴‐Aminocytidine Residue and an Abasic Site