Metal-stabilized rare tautomers of nucleobases.  1.  Iminooxo form of cytosine:  formation through metal migration and estimation of the geometry of the free tautomer

Lippert, Bernhard; Schoellhorn, H.; Thewalt, Ulf

doi:10.1021/ja00281a027

Cited by 100 publications

(50 citation statements)

References 4 publications

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“…Metal migration has been observed in a few cases of platinated bases, nucleosides, and dinucleotides (25,(29)(30)(31) and in one platinated oligonucleotide (24). The 1,3-intrastrand cross-link between G6 and G8 in the trans-DDP-modified d(TC-TACGCGTTCT) rearranges to the 1,4-intrastrand cross-link between C5 and G8 (24).…”

Section: Resultsmentioning

confidence: 99%

DNA double helix promotes a linkage isomerization reaction in trans-diamminedichloroplatinum(II)-modified DNA.

Dalbiès

Payet

Leng

1994

Proc. Natl. Acad. Sci. U.S.A.

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In the reaction between trans-diamminedichloroplatinum(II) and a single-stranded pyrimidinerich oligodeoxyribonucleotide (22-mer) containing the central sequence TGAGT, the 1,3-trans-{Pt(NH3)2[d(GAG)J} crosslink is formed. The 1,3-intrastrand cross-link is inert within the single-stranded oligonucleotide. In contrast, it rearranges to an interstrand cross-link when the platinated oligonucleotide is paired with its complementary deoxyribo-or ribonucleotide strand. The half-life of the 1,3-intrastrand cross-link, -6 h at 370C, is independent of the nature and concentration of the salt (NaCl or NaCI04). It is not dramatically affected when the intervening adenine residue between the chelated guanine residues is replaced by a cytosine or a thymine residue or when the TA base pair adjacent to the 5' or 3' side of the adduct is replaced by a C-G base pair. On the other hand, a mismatch on the 3' or 5' side of the adduct prevents the rearrangement. We propose that the linkage isomerization reaction results from a direct nucleophilic attack of the cytosine residue complementary to the platinated 5' guanine residue on the platinum residue. Among others, the potential use of the DNA RNApromoted reaction is discussed in the context of the antisense strategy to irreversibly cross-link the antisense oligonucleotides to their targets. cis-Diamminedichloroplatinum(II) (cis-DDP) is a chemotherapeutic agent used largely in the clinical treatment of tumors. It is generally accepted that the cytotoxic action of cis-DDP is related to its ability to bind to cellular DNA and form covalent adducts. Although the major lesion is an intrastrand cross-link between two guanine (G) residues, it is not yet established that this lesion is responsible for the antitumor activity of cis-DDP (for general reviews, see refs. 1-4). Acquired resistance to cis-DDP may be associated with the increased gene-specific DNA repair efficiency of the interstrand adducts (5), a minor lesion in which the two G residues in the d(GC)-d(GC) site are cross-linked (6, 7).A question still under debate concerns trans-dichlorodiammineplatinum(II) (trans-DDP), the stereoisomer of cis-DDP. This compound is less mutagenic and less cytotoxic than cis-DDP and is ineffective as an antitumor drug (1)(2)(3)(4). In their reaction with DNA, the two isomers present similarities and differences (for general reviews, see refs. 8 and 9). The DNA modification by cis-or trans-DDP is controlled kinetically and the adducts are formed in two solvent-assisted reactions. The exchange of the chloro groups of both isomers is rate-limiting in both the initial attack of DNA and the closure of monofunctional adducts to bifunctional crosslinks. The preferred site of initial binding of the isomers is the N7 atom of G residues. Subsequently, the monofunctional adducts react with the neighboring bases to form intrastrand and interstrand cross-links. Among the differences between the two isomers, one is that stereochemical limitations preclude trans-DDP from forming intrastrand cross-links b...

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Section: Resultsmentioning

confidence: 99%

DNA double helix promotes a linkage isomerization reaction in trans-diamminedichloroplatinum(II)-modified DNA.

Dalbiès

Payet

Leng

1994

Proc. Natl. Acad. Sci. U.S.A.

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“…Of particular interest were their interactions with amino acids (Fan et al, 2010;Samijlenko et al, 2001Samijlenko et al, , 2004Stepanyugin et al, 2002aStepanyugin et al, , 2002b and protons or alkali metal cations (Lippert et al, 1986;Lippert & Gupta, 2009;Samijlenko et al, 2010;Šponer et al, 2001), as the extra positive charge could stabilize the structure of rare tautomers through an intramolecular salt bridge. Moreover, the coordination of metal ions to nucleobases is known to lead frequently to the stabilization of rare tautomeric forms (Burda et al, 2000;Lippert et al, 1986;Lippert & Gupta, 2009;Samijlenko et al, 2010), with numerous examples reported for various nucleobases (Lippert & Gupta, 2009;Lippert et al, 1986;Schoellhorn et al, 1989;Renn et al, 1991;Zamora et al, 1997). In these metal-stabilized rare tautomers, the metal is located at a position that is usually occupied by a proton, forcing the proton to move to another position and thereby generating the rare tautomer.…”

Section: Tautomerisation Of the Dna Bases In Dimersmentioning

confidence: 99%

Elementary Molecular Mechanisms of the Spontaneous Point Mutations in DNA: A Novel Quantum-Chemical Insight into the Classical Understanding

Brovarets’¹,

Kolomiets²,

Hovorun³

2012

Quantum Chemistry - Molecules for Innovations

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“…4, 5 Reactions of metal ions with nucleobases, hence with mixtures containing an excess of the preferred major tautomer and a tiny amount of the rare tautomer, can lead to a product containing exclusively the minor tautomer.…”

Section: Introductionmentioning

confidence: 99%

Concentration dependent tautomerism in green [Cu(HL1)(L2)] and brown [Cu(L1)(HL2)] with H2L1 = (E)-N′-(2-hydroxy-3-methoxybenzylidene)benzoylhydrazone and HL2 = pyridine-4-carboxylic (isonicotinic) acid

et al. 2011

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Metal-stabilized rare tautomers of nucleobases. 1. Iminooxo form of cytosine: formation through metal migration and estimation of the geometry of the free tautomer

Cited by 100 publications

References 4 publications

DNA double helix promotes a linkage isomerization reaction in trans-diamminedichloroplatinum(II)-modified DNA.

DNA double helix promotes a linkage isomerization reaction in trans-diamminedichloroplatinum(II)-modified DNA.

Elementary Molecular Mechanisms of the Spontaneous Point Mutations in DNA: A Novel Quantum-Chemical Insight into the Classical Understanding

Concentration dependent tautomerism in green [Cu(HL1)(L2)] and brown [Cu(L1)(HL2)] with H2L1 = (E)-N′-(2-hydroxy-3-methoxybenzylidene)benzoylhydrazone and HL2 = pyridine-4-carboxylic (isonicotinic) acid

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