A Stable DNA Duplex Containing a Non-Hydrogen-Bonding and Non-Shape-Complementary Base Couple: Interstrand Stacking as the Stability Determining Factor

Brotschi, Christine; Häberli, Adrian; Leumann, Christian J.

doi:10.1002/1521-3773(20010817)40:16<3012::aid-anie3012>3.0.co;2-y

Cited by 112 publications

(57 citation statements)

References 31 publications

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“…Clearly, 4 fits best as an artificial DNA base into the base stack. Except in the case of indole, the destabilization introduced by our C-nucleosides is similar to those previously reported for, for example, bipyridines 39 or binaphthyls. 40 Nucleoside 4 fits into a new generation of nucleoside mimics that form metal-mediated base pairs as mentioned in the introduction.…”

Section: Biographicalsupporting

confidence: 87%

Organic Chemistry of DNA Functionalization; Chromophores as DNA Base Substitutes versus DNA Base/2′-Modifications

Schmucker¹,

Wagenknecht²

2012

Synlett

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Nucleic acids are suitable scaffolds for the precise arrangement of different kinds of artificial functionalities inside or along the double helix. In this account, we summarize our synthetic efforts over the last ten years to modify DNA chemically with organic chromophores, fluorescent probes, and metal-ion ligands. We used three different approaches: (i) replacement of DNA bases (substitutes/surrogates), (ii) modifications of DNA bases (mainly 2′-deoxyuridine), and (iii) sugar modifications at the 2′-position. The first two types of modifications were achieved mainly by the DNA building block approach, whereas the latter type is based on postsynthetic methodologies. The different synthetic concepts are described and the influence of representative modifications on the melting temperature is compared. IntroductionDNA plays the central biological role since it encodes the genetic information of all living organisms. Beside its biological functionality, DNA represents an increasingly important structural scaffold for the development of architectures and materials in nanosciences. Nucleic acids are suitable scaffolds for the precise arrangement of different kinds of artificial functionalities inside or along the double helix, such as chromophores, metal-ligand complexes, spin labels, and others. 1-6 The following key features make nucleic acids so attractive in this context: 7 (i) Selfassembly: Encoded by the canonical base pairing, two oligonucleotides assemble spontaneously into double helical or more complex tertiary structures. (ii) Geometry: Due to the base-to-base distance, double helical structures of the A-and B-type provide the ideal basis for photophysical interactions of functionalities inside or along the helix.(iii) Synthesis: Automated oligonucleotide chemistry makes DNA available in any desired base sequence and also in sufficient quantities. (iv) Structural and conformational modulations: Artificial backbones, such as peptide nucleic acids (PNA), 8 typically used in the antisense technology, represent tools to alter the double helical geometries. Moreover, conformation of the oligonucleotides can be modulated by, for example, locked nucleic acids (LNA 9 ) or pyrrolidinyl PNA. 10 (v) Hierarchically structured complexity: Highly complex tertiary and other folded structures can be realized purely based on DNA, such as 2D networks, 11 3D objects, 12 and DNA origami. 13The great advantage of nucleic acids from a synthetic organic chemistry point of view is that they are synthesized by building blocks. In this bottom-up approach, artificial functionalities can be introduced synthetically into nanoarchitectures by providing the corresponding artificial DNA building blocks. 14 Moreover, if building blocks are not synthetically obtainable, postsynthetic methodologies allow the modification of oligonucleotides. This is especially important for functionalities that are not compatible with the broadly applied phosphoramidite chemistry. 15,16 In the last few years, polymerase-assisted biochemical synthesis of ...

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Section: Biographicalsupporting

confidence: 87%

Organic Chemistry of DNA Functionalization; Chromophores as DNA Base Substitutes versus DNA Base/2′-Modifications

Schmucker¹,

Wagenknecht²

2012

Synlett

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“…This effect was observed in earlier studies with non-hydrogen bonding base surrogates and was found to be an enthalpy driven process induced by the increased hydrophobic interactions of such base surrogates. [11,15] An expected decrease in stability was observed for duplexes containing electron donating groups and vice versa a stabilization of duplexes containing electron withdrawing groups. Circular dichroism (CD) spectroscopy revealed that the secondary structure of natural DNA is not disturbed by the phenanthrenyl or pyrenyl modifications.…”

Section: Nh2mentioning

confidence: 96%

Modulation of Excess Electron Transfer through LUMO Gradients in DNA Containing Phenanthrenyl Base Surrogates

Roethlisberger

Kaliginedi

Leumann

2017

Chemistry A European J

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The modulation of excess electron transfer (EET) within DNA containing a dimethylaminopyrene (C-AP) as an electron donor and 5-bromouracil ( Br dU) as a electron acceptor through phenanthrenyl pairs (phen-R) could be achieved by modifying the phenanthrenyl base surrogates with electron withdrawing and donating groups. Arranging the phenanthrenyl units to form a descending LUMO gradient increased the EET efficiency compared to the electron transfer through uniform LUMOs or an ascending LUMO gradient.The well-defined double helical structure of DNA with the linear arranged base pairs represents a suitable scaffold for charge transfer and is therefore subject to intense studies in DNA damage, [1] sensors [2] and applications in molecular electronics.[3]The reductive electron transfer also called excess electron transfer (EET) in DNA is a process that is directed through the lowest unoccupied molecular orbital (LUMO) of the DNA bases. Investigations elucidated that the charge transfer over longer distances occurs via electron hopping mostly through thymine bases (k = 10 10 s -1). [4] In earlier studies it was shown that the replacement of the natural base pairs by non-hydrogen bonding base surrogates with extended aromatic surfaces such as phenanthrene could have beneficial conducting properties and could overcome the physico-chemical limitations of the natural nucleobases.[5] Regarding the reduction of such base surrogates the choice of the electron injector is crucial for the success of the experiments. Investigations by Grigorenko et. al. revealed that pyrene ( Py dU, Ered* = -2.2 V vs NHE) [6] only enables a superexchange mechanism, whereas phenothiazine (PTZ, Ered* = -2.7 V vs SCE) [7] allowed to trigger the system into an electron hopping mechanism with a transport that spreads over longer distances.[5] A photoexcitable dimethyl amino-pyrenyl donor attached to a deoxyuracil ( AP dU, Ered* = -2.2 V vs NHE) [8] that exhibits suitable redox properties for long range charge transfer experiments was successfully used by Bätzner et. al. to inject an electron in hydroquinoline base surrogates. [9] In this study, we investigated the EET through DNA containing phenanthrenyl base surrogates with different reduction potentials and LUMO energy levels. It is believed that the electron transfer within DNA can be modulated by the installation of a potential energy gradient.[10] The predicted advantage of such a redox/LUMO gradient was envisioned to be the unidirectionality of the electron transfer and therefore a gain in efficiency. The installation of the different reduction potentials was deemed to be possible by the introduction of electron withdrawing (CN) and donating (NH2) groups at the 7-position of the phenanthrene (phen). The synthesis of the NH2 phen and phen phosphoramidites applicable for automated DNA synthesis was performed according to published procedures.[11] The introduction of a cyano group required a palladium catalyzed substitution of the intermediate 9 with copper-(I)-cyanide. Tritiylation and phosphiti...

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“…The aromatic nature of the artificial nucleobases is crucial for obtaining a stable duplex through p-stacking, although the dsDNA is remarkably flexible, tolerating and accommodating artificial bases that are not perfect mimics of the natural bases. The thermal analysis and structural solution by NMR spectroscopy of multiple bi-phenyl modified dsDNA by Leumann demonstrates for the first time that interstrand stacking can increase duplex stability, 34 and hydrogen bonding between the natural bases is not crucial in these systems. 35 Multiple insertions of these base-surrogates lead to a zipper-like arrangement (Fig.…”

Section: Artificial Nucleobasesmentioning

confidence: 99%

DNA as supramolecular scaffold for functional molecules: progress in DNA nanotechnology

et al. 2011

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Oligonucleotides have recently gained increased attraction as a supramolecular scaffold for the design and synthesis of functional molecules on the nanometre scale. This tutorial review focuses on the recent progress in this highly active field of research with an emphasis on covalent modifications of DNA; non-covalent interactions of DNA with molecules such as groove binders or intercalators are not part of this review. Both terminal and internal modifications are covered, and the various points of attachment (nucleobase, sugar moiety or phosphodiester backbone) are compared. Using selected examples of the recent literature, the diversity of the functionalities that have been incorporated into DNA strands is discussed.

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A Stable DNA Duplex Containing a Non-Hydrogen-Bonding and Non-Shape-Complementary Base Couple: Interstrand Stacking as the Stability Determining Factor

Cited by 112 publications

References 31 publications

Organic Chemistry of DNA Functionalization; Chromophores as DNA Base Substitutes versus DNA Base/2′-Modifications

Organic Chemistry of DNA Functionalization; Chromophores as DNA Base Substitutes versus DNA Base/2′-Modifications

Modulation of Excess Electron Transfer through LUMO Gradients in DNA Containing Phenanthrenyl Base Surrogates

DNA as supramolecular scaffold for functional molecules: progress in DNA nanotechnology

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