Reactions of Adenosine with Bromo- and Chloromalonaldehydes in Aqueous Solution: Kinetics and Mechanism

Mikkola, Satu; Koissi, Niangoran; Ketomäki, Kaisa; Rauvala, Susanna; Neuvonen, Kari; Lönnberg, Harri

doi:10.1002/1099-0690(200006)2000:12<2315::aid-ejoc2315>3.0.co;2-g

Cited by 15 publications

(11 citation statements)

References 30 publications

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“…No clear evidence for the formation of the corresponding formyletheno products could be obtained, in contrast to the situation with 9-methyladenine. 18 In addition to the signals of the etheno derivatives, three UV-absorbing peaks appeared. The one with t R 4.2 min predominated during the early stages of the reaction (Fig.…”

Section: Product Analysesmentioning

confidence: 99%

“…1 Reactions of nucleophilic amine functions with electrophiles block the normal hydrogen bonding within double-helical DNA, resulting in miscoding during the DNA synthesis and, hence, formation of a mutation. Cyclic DNA adducts obtained by reactions with bifunctional electrophiles, such as malondialdehyde, 2-4 acrolein, 5-8 crotonaldehyde, 7-10 halogenated acetaldehydes, 11-15 halogenated malondialdehydes, [16][17][18] vinyl chloride and chlorooxirane, [19][20][21] and mucohalo acids, [22][23][24][25] have been extensively studied over several decades. Such studies serve a dual purpose.…”

Section: Introductionmentioning

confidence: 99%

“…Some cyclic DNA adducts, such as 1,N 6 -ethenoadenine, 12, 32 3,N 4 -ethenocytocine, 32 N 2 ,3-ethenoguanine, 33 and 1,N 2 -propenoguanine, 2-4 are fluoresescent and can be used as biomarkers. 3,12,16,32,33 Reactions between nucleic acid bases and malondialdehydes, 28 halogenated malondialdehydes 18 and their congener, triformylmethane, [34][35][36] have previously been studied in our laboratory. The reaction of bromomalondialdehyde (BMA) with adenosine has been shown to yield, under slightly acidic conditions, two products, viz.…”

Section: Introductionmentioning

confidence: 99%

“…1,N 6 -ethenoadenosine and its formyl derivative, suggested to be formed via a common acyclic intermediate. 18 As a continuation of the mechanistic work on the reactions of halogenated malondialdehydes with nucleic acid bases, the present work studies the reactions of BMA with 9-substituted guanines. It has been reported that 1,N 2 -etheno and 1,N 2 -formyletheno 25 products are formed in reactions with 3-chloro-4-dichloromethyl-5-hydroxy-2(5H )-furanone, similar to the situation with adenine nucleosides.…”

Section: Introductionmentioning

confidence: 99%

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Reactions of 9-substituted guanines with bromomalondialdehyde in aqueous solution predominantly yield glyoxal-derived adducts

et al. 2004

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Reactions of 9-ethylguanine, 2'-deoxyguanosine and guanosine with bromomalondialdehyde in aqueous buffers over a wide pH-range were studied. The main products were isolated and characterized by (1)H and (13)C NMR and mass spectroscopy. The final products formed under acidic and basic conditions were different, but they shared the common feature of being derived from glyoxal. Among the 1 : 1 adducts, 1,N(2)-(trans-1,2-dihydroxyethano)guanine adduct (6) predominated at pH < 6 and N(2)-carboxymethylguanine adduct (10a,b) at pH > 7. In addition to these, an N(2)-(4,5-dihydroxy-1,3-dioxolan-2-yl)methylene adduct (11a,b) and an N(2)-carboxymethyl-1,N(2)-(trans-1,2-dihydroxyethano)guanine adduct (12) were obtained at pH 10. The results of kinetic experiments suggest that bromomalondialdehyde is significantly decomposed to formic acid and glycolaldehyde under the conditions required to obtain guanine adducts. Glycolaldehyde is oxidized to glyoxal, which then modifies the guanine base more readily than bromomalondialdehyde. Besides the glyoxal-derived adducts, 1,N(2)-ethenoguanine (5a-c) and N(2),3-ethenoguanine adducts (4a-c) were formed as minor products, and a transient accumulation of two unstable intermediates, tentatively identified as 1,N(2)-(1,2,2,3-tetrahydroxypropano)(8) and 1,N(2)-(2-formyl-1,2,3-trihydroxypropano)(9) adducts, was observed.

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Section: Product Analysesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Reactions of 9-substituted guanines with bromomalondialdehyde in aqueous solution predominantly yield glyoxal-derived adducts

et al. 2004

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“…Adenosine and 9-methyladenine, for example, give the respective 3H-imidazo[2,1-i]purine and 3H-imidazo[2,1-i]purine-7carbaldehyde derivatives. 22 Both have been suggested to be formed through a common intermediate, viz. an acyclic carbinolamine that still contains the halogen substituent.…”

Section: Introductionmentioning

confidence: 99%

Solid-phase synthesis of 7-substituted 3H-imidazo[2,1-i]purines

Karskela

Lönnberg

2006

Org. Biomol. Chem.

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A method for solid-supported synthesis of N,N-disubstituted (3H-imidazo[2,1-i]purin-7-yl)methyl amines has been developed. The key features of this library synthesis are: (i) immobilization of commercially available N6-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxyadenosine 3'-(2-cyanoethyl N,N-diisopropylphosphoramidite) by phosphitylation to a hydroxyl-functionalized support, (ii) quantitative conversion of the deprotected adenine base to 3H-imidazo[2,1-i]purine-7-carbaldehyde with bromomalonaldehyde in DMF in the presence of formic acid and 2,6-lutidine, (iii) reductive amination of the formyl group followed by N-alkylation or N-acylation, and (iv) release from the support by acidolytic cleavage of the N-glycosidic bond. Steps (ii) and (iii) have been optimized in some detail by using (adenin-9-yl)acetic acid anchored to a Phe-Wang resin as a model compound.

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The P(III)‐Amidite Based Synthesis of Stable Isotope Labeled mRNA‐Cap‐Structures Enables their Sensitive Quantitation from Brain Tissue

Ripp,

Krämer,

Barth

et al. 2024

Angewandte Chemie

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The 5’ cap structure is crucial to mRNA function, with its diverse methylation patterns depending on the cellular state. Sensitive analytical methods are sought after to quantify this cap variety also referred to as cap epitranscriptome. To address a bottleneck for accurate and precise quantitation, we report a facile and fast access to high‐quality synthetic standards via a new route, involving P(III)‐amidite chemistry. A range of cap nucleotides and their stable heavy isotopic labeled analogues were derived from nucleoside diphosphates, which themselves were directly prepared in a one‐step reaction sequence starting from unprotected nucleosides using a triphosphorylating reagent in combination with ethylenediamine. Considering a wider scope, the route also enables direct access to magic spot nucleotides and diphosphates of isoprenyl‐alcohols. Stable‐isotope labeled cap nucleotides derived from this route paved the way for the development of a highly sensitive LC‐MS/MS method, applied to the characterization of mouse brain cap epitranscriptomes, which turned out to be very different from those of cultured cell lines of widespread use in the life sciences.

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Reactions of Adenosine with Bromo- and Chloromalonaldehydes in Aqueous Solution: Kinetics and Mechanism

Cited by 15 publications

References 30 publications

Reactions of 9-substituted guanines with bromomalondialdehyde in aqueous solution predominantly yield glyoxal-derived adducts

Reactions of 9-substituted guanines with bromomalondialdehyde in aqueous solution predominantly yield glyoxal-derived adducts

Solid-phase synthesis of 7-substituted 3H-imidazo[2,1-i]purines

The P(III)‐Amidite Based Synthesis of Stable Isotope Labeled mRNA‐Cap‐Structures Enables their Sensitive Quantitation from Brain Tissue

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