Connectivity patterns and rotamer states of nucleobases determine acid–base properties of metalated purine quartets

Lüth, Marc Sven; Freisinger, Eva; Kampf, Gunnar; Añorbe, Marta Garijo; Griesser, Rolf; Operschall, Bert P.; Sigel, Helmut; Lippert, Bernhard

doi:10.1016/j.jinorgbio.2015.02.004

Cited by 8 publications

(4 citation statements)

References 112 publications

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“…Unlike 9-methylguanine, for which only the N 7 platinum adduct is commonly reported, [38][39][40][41][42][43] both the N 7 and N 1 positions of adenine [44][45][46][47][48] frequently form adducts with platinum. We therefore inferred that the two species observed by HPLC correspond to N 1 and N 7 linkagei somers of the platinatedn ucleobase.…”

Section: Structural Characterization Of 9-methyladenine Adductsof Phementioning

confidence: 99%

Nucleotide Binding Preference of the Monofunctional Platinum Anticancer‐Agent Phenanthriplatin

Riddell

Johnstone

Park

et al. 2016

Chemistry A European J

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The monofunctional platinum anticancer agent phenanthriplatin generates covalent adducts with the purine bases guanine and adenine. Preferential nucleotide binding was investigated using a polymerase stop assay and linear DNA amplification with a 163-base pair DNA double helix. Like cisplatin, phenanthriplatin forms the majority of adducts at guanosine residues, but significant differences in both the number and position of platination sites emerge when comparing results for the two complexes. Notably, the monofunctional complex generates a greater number of polymerasehalting lesions at adenosine residues than does cisplatin. Studies with 9-methyladenine reveal that, under abiological conditions, phenanthriplatin binds to the N1 or N7 position of 9-methyladenine in approximately equimolar amounts. By contrast, comparable reactions with 9-methylguanine afforded only the N7-bound species. Both of the 9-methyladenine linkage isomers (N1 and N7) exist as two diastereomeric species arising from hindered rotation of the aromatic ligands about their respective platinum–nitrogen bonds. Eyring analysis of rate constants extracted from variable temperature NMR spectroscopic data revealed that the activation energies for ligand rotation in the N1 bound platinum complex and the N7 linkage isomers are comparable. Finally, a kinetic analysis indicated that phenanthriplatin reacts more rapidly by a factor of eight with 9-methylguanine than with 9-methyladenine, suggesting that the distribution of lesions formed on double-stranded DNA is kinetically controlled. In addition, implications for the potent anticancer activity of phenanthriplatin are discussed herein.

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Section: Structural Characterization Of 9-methyladenine Adductsof Phementioning

confidence: 99%

Nucleotide Binding Preference of the Monofunctional Platinum Anticancer‐Agent Phenanthriplatin

Riddell

Johnstone

Park

et al. 2016

Chemistry A European J

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“…A final option to overcome the repulsive interactions of endocyclic N atoms of the purine bases is the introduction of linearly coordinating transition metal ions such as Ag + and Hg 2+ or metal entities such as trans -(NH 3 ) 2 Pt II . Metalated purine base pairs interacting through hydrogen bond formation or open and closed purine quartets containing three or more metal ions have been isolated and X-ray structurally characterized in numerous cases [ 16 – 23 ]. Although of interest from a conceptual point of view, we do not consider these constructs viable models for biologically relevant entities at this point.…”

Section: Resultsmentioning

confidence: 99%

“…Here we focus on the potential of adenine (A) and guanine to form mixed AGAG tetrads in the absence or presence of alkali metal ions and/or under low pH conditions, when A becomes protonated (AH + ). The motivation for this study comes from our earlier findings that a G(AH)(AH)G quartet can be crystallized by employing model nucleobases [ 15 ] and that metal ions capable of cross-linking purine bases via N7 and/or N1 sites enable the construction of metalated purine quartets or fragments thereof, with additional inter-nucleobase hydrogen bonds possible [ 16 – 23 ]. More recent findings on the existence of G 3 triplets layered on G 4 , without [ 24 ] or with a water molecule substituting for the fourth G [ 25 ] and providing a site for binding another flat molecule, as well as mixed G 2 , xanthine, 8-oxoguanine quartets [ 26 , 27 ] justify our approach.…”

Section: Introductionmentioning

confidence: 99%

Mixed guanine, adenine base quartets: possible roles of protons and metal ions in their stabilization

et al. 2017

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Structural variations of the well-known guanine quartet (G4) motif in nucleic acid structures, namely substitution of two guanine bases (G) by two adenine (A) nucleobases in mutual trans positions, are discussed and studied by density functional theory (DFT) methods. This work was initiated by three findings, namely (1) that GA mismatches are compatible with complementary pairing patterns in duplex-DNA structures and can, in principle, be extended to quartet structures, (2) that GA pairs can come in several variations, including with a N1 protonated adeninium moiety (AH), and (3) that cross-linking of the major donor sites of purine nucleobases (N1 and N7) by transition metal ions of linear coordination geometries produces planar purine quartets, as demonstrated by some of us in the past. Here, possible structures of mixed AGAG quartets both in the presence of protons and alkali metal ions are discussed, and in particular, the existence of a putative four-purine, two-metal motif.Electronic supplementary materialThe online version of this article (10.1007/s00775-017-1507-7) contains supplementary material, which is available to authorized users.

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“…There are, at least, two additional aspects, that deserve mentioning in the context of this review: First, and related to 3.3, this work has demonstrated that enormous acidifications of exocyclic amino groups of (metal-carrying) nucleobases is achieved by favorable H bonding interactions with exocyclic functions of adjacent (and metal-cross-linked) nucleobases which stabilize the deprotonated site [37,191]. Measured nucleobase acidifications equal or exceed those of N-methylation or N-protonation substantially and can reach up to 9 log units in the case of adenine nucleobases.…”

Section: Uses Of Trans-[pt(a) 2 (Nb)x]mentioning

confidence: 97%

Beyond Sole Models for the First Steps of Pt-Dna Interactions: Fundamental Properties of Mono(Nucleobase) Adducts of Ptii Coordination Compounds

Lippert¹,

Miguel²

2022

SSRN Journal

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Connectivity patterns and rotamer states of nucleobases determine acid–base properties of metalated purine quartets

Cited by 8 publications

References 112 publications

Nucleotide Binding Preference of the Monofunctional Platinum Anticancer‐Agent Phenanthriplatin

Nucleotide Binding Preference of the Monofunctional Platinum Anticancer‐Agent Phenanthriplatin

Mixed guanine, adenine base quartets: possible roles of protons and metal ions in their stabilization

Beyond Sole Models for the First Steps of Pt-Dna Interactions: Fundamental Properties of Mono(Nucleobase) Adducts of Ptii Coordination Compounds

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