Polycyclic Aromatic DNA‐Base Surrogates: High‐Affinity Binding to an Adenine‐Specific Base‐Flipping DNA Methyltransferase

Beuck, Christine; Singh, Ishwar; Bhattacharya, Anupam; Hecker, Walburga; Parmar, Virinder S.; Seitz, Oliver; Weinhold, Elmar G.

doi:10.1002/anie.200219972

Cited by 74 publications

(53 citation statements)

References 17 publications

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“…Along the lines, it is interesting to note that placement of pyrene-functionalized C -glycosides in DNA duplexes opposite of abasic sites, which are generated via enzyme-mediated extrahelical flipping of the opposing nucleotide, is known to be stabilizing. 58–59 …”

Section: Resultsmentioning

confidence: 99%

C2′-Pyrene-Functionalized Triazole-Linked DNA: Universal DNA/RNA Hybridization Probes

Hrdlicka

2011

J. Org. Chem.

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Development of universal hybridization probes, i.e., oligonucleotides displaying identical affinity toward matched and mismatched DNA/RNA targets, has been a longstanding goal due to potential applications as degenerate PCR primers and microarray probes. The classic approach toward this end has been the use of ‘universal bases’ that either are based on aromatic base analogs without hydrogen-bonding capabilities or hydrogen-bonding purine derivatives. However, development of probes that enable truly ‘universal’ hybridization without compromising duplex thermostability has proven challenging. Here we have used the ‘click reaction’ to synthesize four C2′-pyrene-functionalized triazole-linked 2′-deoxyuridine phosphoramidites. We demonstrate that oligodeoxyribonucleotides modified with the corresponding monomers display: a) minimally decreased thermal affinity toward DNA/RNA complements relative to reference strands; b) highly robust universal hybridization characteristics (average differences in thermal denaturation temperatures of matched vs mismatched duplexes are < 1.5 °C); and c) exceptional affinity toward DNA targets containing abasic sites opposite of the modification site (ΔTm up to +25 °C). The latter observation, along with results from absorption and fluorescence spectroscopy, indicates that the pyrene moiety is intercalating into the duplex whereby the opposing nucleotide is pushed into an extrahelical position. These properties render C2′-pyrene-functionalized triazole-linked DNA as promising universal hybridization probes for applications in nucleic acid chemistry and biotechnology.

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Section: Resultsmentioning

confidence: 99%

C2′-Pyrene-Functionalized Triazole-Linked DNA: Universal DNA/RNA Hybridization Probes

Hrdlicka

2011

J. Org. Chem.

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“…Pyrene as an artificial DNA base sur-rogate has previously been used as a fluoroside [30] and in the investigation of DNA-protein interactions. [31] The 2PydU modification represents a pyrene label that retains the unique and characteristic optical properties of the pyrene chromophore and connects it, but does not couple it electronically, to the DNA base. The chromophore shows the ability for Watson-Crick base-pairing inside DNA, as revealed by the absorption and fluorescence spectra.…”

Section: Discussionmentioning

confidence: 99%

Synthesis of 5‐(2‐Pyrenyl)‐2′‐deoxyuridine as a DNA Modification for Electron‐Transfer Studies: The Critical Role of the Position of the Chromophore Attachment

Wanninger-Weiß

Wagenknecht

2007

Eur J Org Chem

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Keywords: Electron transfer / Fluorescence / Iridium / Oligonucleotides / Palladium / Pyrene 5-(2-Pyrenyl)-2Ј-deoxyuridine (2PydU, 2) has been prepared as a new thymidine analogue in which the 2-position of the pyrene chromophore is connected covalently to the 5-position of uridine through a single C-C bond. The synthesis of 2 starts with the conversion of pyrene (3) into 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrene (4) by using an Ir catalyst that was prepared in situ from [IrCl(cod)] 2 and 4,4Ј-di-tert-butyl-2,2Ј-bipyridine (dtbpy) in the presence of NaOMe. The subsequent Suzuki-Miyaura cross-coupling of 4 with 5-iodo-2Ј-deoxyuridine (5) was performed by using 1,1Ј-bis[(diphenylphosphanyl)ferrocene]dichloropalladium-(II) as the catalyst in a THF/MeOH/H 2 O mixture as the solvent. The modified nucleoside 2 was characterized by absorption and fluorescence spectroscopy. The results were compared with the strongly electronically coupled 5-(1-pyrenyl)-2Ј-deoxyuridine (1PydU, 1). Finally, the nucleoside 2 was converted into the corresponding phosphoramidite 7 as a DNA building block. The DNA set 8a-8d was synthesized

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“…However, it is known that the interaction with a strong stacking group often disrupts the helical structure of DNA. For example, planar polycyclic surrogates possessing fused 1–3 aromatic rings or more intercalate into a DNA duplex and perturbs the helix conformation [20–23]. The covalently appended quinoline residue at the terminal of an oligonucleotide also largely disrupts the DNA duplex structure [24].…”

Section: Unnatural Nucleosides That Mimic Nucleotide Basesmentioning

confidence: 99%

Use of Nucleic Acid Analogs for the Study of Nucleic Acid Interactions

Nakano

Fujii

Sugimoto

2011

Journal of Nucleic Acids

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Unnatural nucleosides have been explored to expand the properties and the applications of oligonucleotides. This paper briefly summarizes nucleic acid analogs in which the base is modified or replaced by an unnatural stacking group for the study of nucleic acid interactions. We also describe the nucleoside analogs of a base pair-mimic structure that we have examined. Although the base pair-mimic nucleosides possess a simplified stacking moiety of a phenyl or naphthyl group, they can be used as a structural analog of Watson-Crick base pairs. Remarkably, they can adopt two different conformations responding to their interaction energies, and one of them is the stacking conformation of the nonpolar aromatic group causing the site-selective flipping of the opposite base in a DNA double helix. The base pair-mimic nucleosides can be used to study the mechanism responsible for the base stacking and the flipping of bases out of a nucleic acid duplex.

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Polycyclic Aromatic DNA‐Base Surrogates: High‐Affinity Binding to an Adenine‐Specific Base‐Flipping DNA Methyltransferase

Cited by 74 publications

References 17 publications

C2′-Pyrene-Functionalized Triazole-Linked DNA: Universal DNA/RNA Hybridization Probes

C2′-Pyrene-Functionalized Triazole-Linked DNA: Universal DNA/RNA Hybridization Probes

Synthesis of 5‐(2‐Pyrenyl)‐2′‐deoxyuridine as a DNA Modification for Electron‐Transfer Studies: The Critical Role of the Position of the Chromophore Attachment

Use of Nucleic Acid Analogs for the Study of Nucleic Acid Interactions

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