Adenine Sites Research Articles

Head‐to‐Head Right‐Handed Cross‐Links of the Antitumor‐Active Bis(μ‐N,N′‐di‐p‐tolylformamidinato)dirhodium(II,II) Unit with the Dinucleotides d(GpA) and d(ApG)

Reactions of cis-[Rh(2)(DTolF)(2)(NCCH(3))(6)](BF(4))(2) with the dinucleotides d(GpA) and d(ApG) proceed to form [Rh(2)(DTolF)(2){d(GpA)}] and [Rh(2)(DTolF)(2){d(ApG)}], respectively, with bridging purine bases spanning the Rh-Rh unit in the equatorial positions. Both dirhodium adducts exhibit head-to-head (HH) arrangement of the bases, as indicated by the presence of H8/H8 NOE cross-peaks in the 2D ROESY NMR spectra. The guanine bases bind to the dirhodium core at positions N7 and O6, a conclusion that is supported by the absence of N7 protonation at low pH values and the notable increase in the acidity of the guanine N1H sites (pK(a) approximately 7.4 in 4:1 CD(3)CN/D(2)O), inferred from the pH-dependence titrations of the guanine H8 proton resonances. In both dirhodium adducts, the adenine bases coordinate to the metal atoms through N6 and N7, which induces stabilization of the rare imino tautomer of the bases with a concomitant substantial decrease in the basicity of the N1H adenine sites (pK(a) approximately 7.0-7.1 in 4:1 CD(3)CN/D(2)O), as compared to the imino form of free adenosine. The presence of the adenine bases in the rare imino form is further corroborated by the observation of DQF-COSY H2/N1H and ROE N1H/N6H cross-peaks in the 2D NMR spectra of [Rh(2)(DTolF)(2){d(GpA)}] and [Rh(2)(DTolF)(2){d(ApG)}] in CD(3)CN at -38 degrees C. The 2D NMR spectroscopic data and the molecular modeling results suggest the presence of right-handed variants, HH1R, in solution for both adducts (HH1R refers to the relative base canting and the direction of propagation of the phosphodiester backbone with respect to the 5' base). Complete characterization of [Rh(2)(DTolF)(2){d(GpA)}] and [Rh(2)(DTolF)(2){d(ApG)}] by 2D NMR spectroscopy and molecular modeling supports anti-orientation of the sugar residues for both adducts about the glycosyl bonds as well as N- and S-type conformations for the 5'- and 3'-deoxyribose residues, respectively.

Mutation spectra induced by 1-nitropyrene 4,5-oxide and 1-nitropyrene 9,10-oxide in the supF gene of human XP-A fibroblasts

1-Nitropyrene 4,5-oxide and 1-nitropyrene 9,10-oxide are oxidative metabolites that are responsible for the mutagenicity of 1-nitropyrene. In this study, the mutation spectra induced by oxidative metabolites in human cells were determined using a shuttle vector assay. The mutation frequencies induced by 1-nitropyrene 9,10-oxide were 2-3 times higher than those induced by 1-nitropyrene 4,5-oxide. The base substitutions induced by 1-nitropyrene 4,5-oxide were G --> A transitions, G --> C transversions, and G --> T transversions. In the case of 1-nitropyrene 9,10-oxide, G --> A transitions, G --> T transversions, A --> G transitions and G --> C transversions were observed. Most base substitution mutations induced by oxidative metabolites occurred at the guanine sites in the supF gene. These sequence-specific hot spots were commonly identified as 5'-GA sequences for both metabolites. On the other hand, the sequence-specific hot spots at the adenine sites were identified as 5'-CAC sequences for 1-nitropyrene 9,10-oxide. These results suggest that the oxidative metabolites of 1-nitropyrene induce sequence-specific DNA mutations at the guanine and adenine sites at high frequency.

Effect of 1-methyladenine on double-helical DNA structures

Methylation at the N1 site of adenine leads to the formation of cytotoxic 1-methyladenine (m1A). Since the N1 site of adenine is involved in the hydrogen bonding of T·A and A·T Watson–Crick base pairs, it is expected that the pairing interactions will be disrupted upon 1-methylation. In this study, high-resolution NMR investigations were performed to determine the effect of m1A on double-helical DNA structures. Interestingly, instead of disrupting hydrogen bonding, we found that 1-methylation altered the T·A Watson–Crick base pair to T( anti)·m1A( syn) Hoogsteen base pair, providing insights into the observed differences in AlkB-repair efficiency between dsDNA and ssDNA.

Reactions of DNA bases with the anti-cancer nitrogen mustard mechlorethamine: A quantum chemical study

Reactions of the aziridinium ion of mechlorethamine ( A Z + 1 ) at the N7, N3 and O6 sites of guanine, N7, N3 and N1 sites of adenine, O2 and N3 sites of cytosine, and O2 and O4 sites of thymine were studied using density functional theory (B3LYP) and the MP2 method in gas phase and aqueous media. The calculations explain the mechanism of alkylation of the DNA bases and show that the reactions of the A Z + 1 ion would be most likely to occur at the N7 site of guanine and the N3 site of adenine while it would be much less likely to occur at the carbonyl oxygen sites of the DNA bases.

Unprecedented Head-to-Head Right-Handed Cross-Links between the Antitumor Bis(μ-N,N‘-di-p-tolylformamidinate) Dirhodium(II,II) Core and the Dinucleotide d(ApA) with the Adenine Bases in the Rare Imino Form

Reactions of the anticancer active compound cis-[Rh2(DTolF)2(CH3CN)6](BF4)2 with 9-ethyladenine (9-EtAdeH) or the dinucleotide d(ApA) proceed with bridging adenine bases in the rare imino form (A*), spanning the Rh-Rh bond at equatorial positions via N7/N6. The inflection points for the pH-dependent H2 and H8 NMR resonance curves of cis-[Rh2(DTolF)2(9-EtAdeH)2](BF4)2 correspond to N1H deprotonation of the metal-stabilized rare imino tautomer, which takes place at pKa approximately 7.5 in CD3CN-d3, a considerably reduced value as compared to that of the imino form of 9-EtAdeH. Similarly, coordination of the metal atoms to the N7/N6 adenine sites in Rh2(DTolF)2{d(ApA)} induces formation of the rare imino tautomer of the bases with a concomitant substantial decrease in the basicity of the N1H sites (pKa approximately 7.0 in CD3CN-d3), as compared to the imino form of the free dinucleotide. The presence of the adenine bases in the rare imino form, due to bidentate metalation of the N6/N7 sites, is further corroborated by DQF-COSY H2/N1H and ROE N1H/N6H cross-peaks in the 2D NMR spectra of Rh2(DTolF)2{d(ApA)} in CD3CN-d3 at -38 degrees C. Due to the N7/N6 bridging mode of the adenine bases in Rh2(DTolF)2{d(ApA)}, only the anti orientation of the imino tautomer is possible. The imino form A* of adenine in DNA may result in AT-->CG transversions or AT-->GC transitions, which can eventually lead to lethal mutations. The HH arrangement of the bases in Rh2(DTolF)2{d(ApA)} is indicated by the H8/H8 NOE cross-peaks in the 2D ROESY NMR spectrum, whereas the formamidinate bridging groups dictate the presence of one right-handed conformer HH1R in solution. Complete characterization of Rh2(DTolF)2{d(ApA)} by 2D NMR spectroscopy and molecular modeling supports the presence of the HH1R conformer, anti orientation of both sugar residues about the glycosyl bonds, and N-type conformation for the 5'-A base.

Systematic Exploration of the Structural Features of Yatakemycin Impacting DNA Alkylation and Biological Activity

A systematic examination of the impact of the yatakemycin left and right subunits and their substituents is detailed along with a study of its unique three subunit arrangement (sandwiched vs extended and reversed analogues). The examination of the ca. 50 analogues prepared illustrate that within the yatakemycin three subunit structure, the subunit substituents are relatively unimportant and that it is the unique sandwiched arrangement that substantially increases the rate and optimizes the efficiency of its DNA alkylation reaction. This potentiates the cytotoxic activity of yatakemycin and its analogues overcoming limitations typically observed with more traditional compounds in the series (CC-1065, duocarmycins). Moreover, a study of the placement of the alkylation subunit within the three subunit arrangement (sandwiched vs extended and reversed analogues) indicates that it not only has a profound impact on the rate and efficiency of DNA alkylation but also controls and establishes the DNA alkylation selectivity as well, where both enantiomers of such sandwiched agents alkylate the same adenine sites exhibiting the same DNA alkylation selectivity independent of their absolute configuration.

Photocatalytic probing of DNA sequence by using TiO 2/dopamine-DNA triads

A method to control charge transfer reaction in DNA using hybrid nanometer-sized TiO 2 nanoparticles was developed. In this system extended charge separation reflects the sequence of DNA and was measured using metallic silver deposition or by photocurrent response. Light-induced extended charge separation in these systems was found to be dependent on the DNA-bridge length and sequence. The yield of photocatalytic deposition of silver was studied in systems having GG accepting sites imbedded in AT runs at varying distances from the TiO 2 nanoparticle surface. Weak distance dependence of charge separation indicative of a hole hopping through mediating adenine (A) sites was found. The quantum yield of silver deposition in the system having a GG accepting site placed 8.5 Å from the nanoparticle surface was found to be Φ = 0.70 (70%) and Φ = 0.56 (56%) for (A) n and (AT) n/2 bridge, respectively. Hole injection to GG trapping sites as far as 70 Å from a nanoparticle surface in the absence of G hopping sites was measured. Introduction of G hopping sites increased the efficiency of hole injection. The efficiency of photocatalytic deposition of metallic silver was found to be sensitive to the presence of a single nucleobase mismatch in the DNA sequence.

Adenine-based receptor for dicarboxylic acids

The adenine-based fluorescent receptor 1 was designed and synthesized for the selective recognition of dicarboxylic acids in CH 3CN. The recognition takes place through the Hoogsteen binding site of adenine with concomitant PET quenching of the anthracene moiety. The carboxylic acid binding to 1 was investigated by 1H NMR, X-ray, UV–vis, and fluorescence spectroscopic methods. The Hoogsteen (HG) cleft of receptor 1 is found to be selective for glutaric acid.

An empirical approach for detecting nucleotide-binding sites on proteins

Protein structure data in the PDB (Protein Data Bank) were used to construct empirical scores of nucleotide-protein interactions. A simple strategy to evaluate the spatial distribution of protein atoms around the base moieties of nucleotides was applied to categorize adenine, guanine, nicotinamide and flavin nucleotide-binding sites. In addition to the known nucleotide-binding motifs, the empirical scores detected several other features that were shared among proteins with different folds. The empirical scores were also used to predict the binding sites on protein molecules and a comprehensive test of the prediction system was performed. As a result, adenine, guanine, nicotinamide and flavin sites were detected with efficiencies of 31, 29, 32 and 40%, respectively. The predictions were judged to be successful if the predicted base with the best score was located within a 3.0 A r.m.s.d. from the known ligand positions.

Simulation of DNA bases in water: Comparison of the Monte Carlo algorithm with molecular mechanics force fields

The interaction between the nucleic acid bases and solvent molecules has an important effect in various biochemical processes. We have calculated total energy and free energy of the solvation of DNA bases in water by Monte Carlo simulation. Adenine, guanine, cytosine, and thymine were first optimized in the gas phase and then placed in a cubic box of water. We have used the TIP3 model for water and OPLS for the nucleic acid bases. The canonical (T, V, N) ensemble at 25 degrees C and Metropolis sampling technique have been used. Good agreement with other available computational data was obtained. Radial distribution functions of water around each site of adenine, guanine, cytosine, and thymine have been computed and the results have shown the ability of the sites for hydrogen bonding and other interactions. The computations have shown that guanine has the highest value of solvation free energy and N7 and N6 in adenine and guanine, N3 in cytosine, and N3 and O4 in thymine have the largest radial distribution function. Monte Carlo simulation has also been performed using the CHARMM program under the same conditions, and the results of two procedures are compared.

CO 2 activation and synthesis of cyclic carbonates and alkyl/aryl carbamates over adenine-modified Ti-SBA-15 solid catalysts

Cyclic carbonates were synthesized by the cycloaddition of CO 2 to epoxides (epichlorohydrin, propene oxide, and styrene oxide), and carbamates were synthesized by reaction of alkyl or aryl amines, CO 2, and n-butyl bromide. Solvents and cocatalysts/promoters like N,N-dimethylaminopyridine (DMAP) and quaternary ammonium salts, which are usually essential with conventional catalyst systems, could be avoided with the use of adenine-modified Ti-SBA-15 catalysts. The catalysts were reused in several recycle experiments. The structural and textural properties of the catalysts were determined by X-ray diffraction (XRD), transmission electron microscopy (TEM), N 2 adsorption, and Fourier transform infrared (FTIR) and diffuse reflectance ultraviolet–visible (UV–vis DRS) techniques. Acid–base properties of the solid catalysts were investigated by temperature-programmed desorption (TPD) of NH 3 and CO 2 and DRIFTIR spectroscopy of adsorbed pyridine and CO 2 techniques. The studies reveal that the Ti 4+ ions increase catalytic activity by enhancing the adsorption of the epoxide and alkyl or aryl amine substrates. CO 2 molecules are activated at the basic nitrogen groups of adenine. Increasing the surface concentrations of either CO 2 (by anchoring basic molecules like adenine or increasing the partial pressure of CO 2) or epoxides and alkyl or aryl amines (by increasing the concentration of Lewis acidic Ti 4+ ions) enhances the catalytic activity. CO 2 molecules activated at the covalently anchored adenine sites react with epoxide/amines adsorbed on the silica surface to form carbonates/carbamates.

Sites of Adsorption of Adenine, Uracil, and Their Corresponding Derivatives on Sodium Montmorillonite

Clay minerals are considered important to chemical evolution processes due to their properties, ancient origin, and wide distribution. To extend the knowledge of their role in the prebiotic epoch, the adsorption sites of adenine, adenosine, AMP, ADP, ATP, Poly A, uracil, uridine, UMP, UDP, UTP and Poly U on sodium montmorillonite are investigated. X-ray diffraction, ultraviolet and infrared spectroscopy studies indicate that these molecules distribute into the interlamellar channel and the edge of the clay crystals. Monomers are adsorbed predominantly in the interlamellar channel, whereas polymers adsorb along the crystal edges. Such behavior is discussed mainly in terms of bulk pH, pK(a) of the adsorbate, and Van der Waals interactions.

Gas-phase acidity studies of multiple sites of adenine and adenine derivatives.

The acidities of multiple sites in the purine nucleobase adenine (1) and adenine alkyl derivatives 9-ethyladenine (2), 3-methyladenine (3), 1-methyladenine (4), and N,N-dimethyladenine (5) have been investigated for the first time, using computational and experimental methods to provide an understanding of adenine reactivity. We have previously measured two acidic sites on adenine, with the N9 site being 19 kcal mol(-)(1) more acidic than the N10 site (333 +/- 2 versus 352 +/- 4 kcal mol(-)(1), respectively). In this work, we have established that 9-ethyladenine has two sites more acidic than water: the N10 (352 +/- 4 kcal mol(-)(1)) and the C8 (374 +/- 2 kcal mol(-)(1)). We have likewise measured two acidities for 3-methyladenine, the N10 (347 +/- 4 kcal mol(-)(1)) and the C2 (370 +/- 3 kcal mol(-)(1)). For 1-methyladenine and N,N-dimethyladenine, we measure the N9H acidity to be 331 +/- 2 and 333 +/- 2 kcal mol(-)(1), respectively. We believe that the bracketing of only one site for the latter species is a kinetic effect, which we discuss further in the paper. Computationally, we have found the interesting result that some of the vinylic C-H sites in these purine bases are predicted to be much more acidic than water (DeltaH(acid) = 390.7 kcal mol(-)(1)) in the gas phase, on the order of 373 kcal mol(-)(1). The acidic vinylic C-H sites are always adjacent to an N-R group, and this pattern is maintained regardless of whether the site is on the five- or six-membered ring of the purine. Vinylic C-H sites elsewhere on the purine have calculated acidities of about 400 kcal mol(-)(1). The differing acidities are interpreted through electrostatic potential calculations. We also relate our results to the intriguing biochemical decarboxylation of orotate ribose monophosphate, which involves a vinylic anion adjacent to an N-R group; this decarboxylation is the last step in the de novo biosynthesis of pyrimidine nucleotides, and the enzyme that catalyzes the reaction, orotate ribose monophosphate decarboxylase, has been the subject of intense study recently, as its mechanism remains elusive.

Electrostatic Potential of Nucleotide-free Protein is Sufficient for Discrimination Between Adenine and Guanine-specific Binding Sites

Despite sharing many common features, adenine-binding and guanine-binding sites in proteins often show a clear preference for the cognate over the non-cognate ligand. We have analyzed electrostatic potential (ESP) patterns at adenine and guanine-binding sites of a large number of non-redundant proteins where each binding site was first annotated as adenine/guanine-specific or non-specific from a survey of primary literature. We show that more than 90% of ESP variance at the binding sites is accounted for by only two principal component ESP vectors, each aligned to molecular dipoles of adenine and guanine. Projected on these principal component vectors, the adenine/guanine-specific and non-specific binding sites, including adenine-containing dinucleotides, show non-overlapping distributions. Adenine or guanine specificities of the binding sites also show high correlation with the corresponding electrostatic replacement (cognate by non-cognate ligand) energies. High correlation coefficients (0.94 for 35 adenine-binding sites and 1.0 for 20 guanine-binding sites) were obtained when adenine/guanine specificities were predicted using the replacement energies. Our results demonstrate that ligand-free protein ESP is an excellent indicator for discrimination between adenine and guanine-specific binding sites and that ESP of ligand-free protein can be used as a tool to annotate known and putative purine-binding sites in proteins as adenine or guanine-specific.

Chemical and enzymatic synthesis of tritium labelled coenzymes

AbstractDetails of the synthesis of tritium labelled co enzymes‐nicotinamide adenine dinucleotide and coenzyme A by isotope exchange and enzymatic reactions are reported. It was established, that among the investigated chemical reactions, the most effective is solid state isotope exchange with gaseous tritium. This method was used to produce [3H] nicotinamide adenine dinucleotide (111 Ci/mmol), [3H] coenzyme A (3.9 Ci/mmol) and D‐[G‐3H] pantothenic acid (43 Ci/mmol). It was shown that most of the tritium in the labeled nicotinamide adenine dinucleotide and coenzyme A was localized in the nicotinamide (98%) and adenine (89%) sites, respectively. For synthesis of coenzymes labelled with tritium at other sites we developed enzymatic methods which used labelled precursors. Optimum conditions for enzymatic synthesis of [adenine‐3H] nicotinamide adenine dinucleotide from [2,8‐3H] ATP and [pantothenate‐3H] coenzyme A from D‐[G‐3H] pantothenic acid were determined. The tritium labelled acetyl coenzyme A was synthesized by acetylation of labelled coenzyme A with acetic anhydride. The methods chosen allow one to produce tritium labelled coenzymes at high specific activity. Copyright © 2003 John Wiley & Sons, Ltd.

Comprehensive model for allosteric regulation of mammalian ribonucleotide reductase: refinements and consequences.

Reduction of NDPs by murine ribonucleotide reductase (mRR) requires catalytic (mR1) and free radical-containing (mR2) subunits and is regulated by nucleoside triphosphate allosteric effectors. Here we present the results of several studies that refine the recently presented comprehensive model for the allosteric control of mRR enzymatic activity [Kashlan, O. B., et al. (2002) Biochemistry 41, 462-474], in which nucleotide binding to the specificity site (s-site) drives formation of an active R1(2)R2(2) dimer, ATP or dATP binding to the adenine site (a-site) drives formation of a tetramer, mR1(4a), which isomerizes to an inactive form, mR1(4b), and ATP binding to the hexamerization site (h-site) drives formation of an active R1(6)R2(6) hexamer. Analysis of the a-site D57N variant of mR1, which differs from wild-type mR1 (wt-mR1) in that its RR activity is activated by both ATP and dATP, demonstrates that dATP activation of the D57N variant RR arises from a blockage in the formation of mR1(4b) from mR1(4a), and provides strong evidence that mR1(4a) forms active complexes with mR2(2). We further demonstrate that (a) differences in the effects of ATP versus dATP binding to the a-site of wt-mR1 provide specific mechanisms by which the dATP/ATP ratio in mammalian cells could modulate in vivo RR enzymatic activity, (b) the comprehensive model is valid over a range of Mg(2+) concentrations that include in vivo concentrations, and (c) equilibrium constants derived for the comprehensive model can be used to simulate the distribution of R1 among dimer, tetramer, and hexamer forms in vivo. Such simulations indicate that mR1(6) predominates over mR1(2) in the cytoplasm of normal mammalian cells, where the great majority of RR activity is located, but that mR1(2) may be important for nuclear RR activity and for RR activity in cells in which the level of ATP is depleted.

Acidity of adenine and adenine derivatives and biological implications. A computational and experimental gas-phase study.

The gas-phase acidities of adenine, 9-ethyladenine, and 3-methyladenine have been investigated for the first time, using computational and experimental methods to provide an understanding of the intrinsic reactivity of adenine. Adenine is found to have two acidic sites, with the N9 site being 19 kcal mol(-1) more acidic than the N10 site; the bracketed acidities are 333 +/- 2 and 352 +/- 4 kcal mol(-1), respectively. Because measurement of the less acidic site can be problematic, we benchmarked the adenine N10 measurement by bracketing the acidity of 9-ethyladenine, which has the N9 site blocked and allows for exclusive measurement of the N10 site. The acidity of 9-ethyladenine brackets to 352 +/- 4 kcal mol(-1), comparable to that of the N10 site of the parent adenine. Calculations and experiments with 3-methyladenine, a harmful mutagenic nucleobase, uncovered the surprising result that the most commonly written tautomer of 3-methyladenine is not the most stable in the gas phase. We have found that the most stable tautomer is the "N10 tautomer" 10, as opposed to the imine tautomer 3. The bracketed acidity of 10 is 347 +/- 4 kcal mol(-1). Since 10 is not a viable species in DNA, 3 is a likely tautomer; calculations indicate that this form has an extremely high acidity (320-323 kcal mol(-1)). The biological implications of these results, particularly with respect to enzymes that cleave alkylated bases from DNA, are discussed.

On the competition of the purine bases, functionalities of peptide side chains, and protecting agents for the coordination sites of dicationic cisplatin derivatives.

The Pt-L bond energies of simple triammineplatinum(II) complexes, [Pt(NH(3))(3)L](2+), with oxygen-, nitrogen-, and sulfur-containing donor ligands L have been predicted and rationalized using density functional theory. The ligands L have been chosen as models for functionalities of peptide side chains, for sulfur-containing protecting agents, and for adenine and guanine sites of the DNA as the ultimate target of platinum anticancer drugs. Calculation of the Pt-L bond energy in [Pt(NH(3))(3)L](2+) reveals that the soft metal center of triammineplatinum(II) prefers N ligands over S ligands. This remarkable result has been discussed in light of several interpretations of the hard and soft acids and bases principle. The concept of orbital-symmetry-based energy decomposition has been employed for the determination of the contributions from sigma and pi orbital interactions, electrostatics, and intramolecular hydrogen bonding to the Pt-L bond energy. The calculations show that considerable differences in the bond energies of the triammineplatinum(II) complexes with N-heterocycles such as 1-methylimidazole, 9-methyladenine, and 9-methylguanine arise from electrostatics rather than from orbital interactions. Surprisingly, the net stabilization by hydrogen bonding between the (Pt)N-H group and the oxygen of 9-methylguanine is as weak as the intramolecular hydrogen bond in the aqua complex [Pt(NH(3))(3)(H(2)O)](2+), challenging the common hypothesis that DNA-active anticancer drugs require carrier ligands with N-H functionalities because of their hydrogen-bonding ability. The influence of a polarizable environment on the stability of the complexes has been investigated systematically with the dependence of the dielectric constant epsilon. With increasing epsilon, the complexes with S-containing ligands are more strongly stabilized than the complexes of the N-containing heterocycles. At epsilon = 78.4, the dielectric constant of water, 9-methylguanine remains the only purine derivative investigated which is competitive to neutral sulfur ligands. These findings are particularly important for a rationalization of the results from recent experimental studies on the competition of biological donor ligands L for coordination with the metal center of [Pt(dien)L](2+) (dien = 1,5-diamino 3-azapentane).

Inner- and outer-sphere binding of the minor groove site of adenine by alkali metal ions

Download options Please wait... Supplementary files Crystal structure data TXT (42K) Article information DOI https://doi.org/10.1039/B108427P Article type Communication Submitted 17 Sep 2001 Accepted 06 Dec 2001 First published 17 Dec 2001 Download Citation J. Chem. Soc., Dalton Trans., 2002, 131-133 BibTex EndNote MEDLINE ProCite ReferenceManager RefWorks RIS Permissions Request permissions Inner- and outer-sphere binding of the minor groove site of adenine by alkali metal ions A. E. Gibson, C. Price, W. Clegg and A. Houlton, J. Chem. Soc., Dalton Trans., 2002, 131 DOI: 10.1039/B108427P To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page. If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given. If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page. Read more about how to correctly acknowledge RSC content. Search articles by author Ashleigh E. Gibson Clayton Price William Clegg Andrew Houlton

Isolation and mass spectrometric characterization of dimeric adenine photoproducts in oligodeoxynucleotides.

UVC irradiation of oligodeoxynucleotides (ODNs) at 254 nm generates two types of DNA photoproducts, A=A and (AA)*, at adjacent adenine sites in DNA. Kumar et al. previously proved the structure of these adducts in dinucleoside monophosphates [Kumar, S., et al. (1987) Nucleic Acids Res. 15, 1199-1216; Kumar, S., et al. (1991) Nucleic Acids Res. 19, 2841-2847]. Product-ion spectra of ESI-produced [M - 2H](2-) ions of the ODNs containing the dimeric adenine photoproducts show distinctive fragmentation that is informative of the structures of the photoproducts. The gas-phase cleavages of ODNs at sites of those photoproducts and thymine thymine or thymine adenine ((TA)*) photoproducts are analogous to cleavages induced by hot alkaline treatment. Nuclease-P1 digestions of ODNs containing dimeric adenine photoproducts give shorter pieces of ODNs bearing the photoproducts, which fragment under collisional activation conditions in a similar way to the large ODNs containing the photoproducts. The tandem mass spectrometric results show that the yield of (AA)* is lower than that of A=A when adjacent adenines are in the middle of an ODN sequence, and the yield of the latter is similar to that of (TA)*.