DNA minor groove hydration probed with 4’-alkylated thymidines

Detmer, Ilka; Summerer, Daniel; Marx, Andreas

doi:10.1039/b207582m

Cited by 13 publications

(13 citation statements)

References 19 publications

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“…The geometries of DNA duplexes are largely determined by H‐bonded nucleobase pairing,161a offset base stacking at a vertical base distance of 3.4 Å, the conformation of the sugar backbone,161b the base sequence, the hydrophobic effect, and presumably specific solvation patterns in the minor and major grooves 161c. The geometries of DNA duplexes have increasingly been subjected to high‐level theoretical calculations, and the results have been summarized in a recent review 162.…”

Section: Arene–arene Interactionsmentioning

confidence: 99%

Interactions with Aromatic Rings in Chemical and Biological Recognition

2003

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Intermolecular interactions involving aromatic rings are key processes in both chemical and biological recognition. Their understanding is essential for rational drug design and lead optimization in medicinal chemistry. Different approaches-biological studies, molecular recognition studies with artificial receptors, crystallographic database mining, gas-phase studies, and theoretical calculations-are pursued to generate a profound understanding of the structural and energetic parameters of individual recognition modes involving aromatic rings. This review attempts to combine and summarize the knowledge gained from these investigations. The review focuses mainly on examples with biological relevance since one of its aims it to enhance the knowledge of molecular recognition forces that is essential for drug development.

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Section: Arene–arene Interactionsmentioning

confidence: 99%

Interactions with Aromatic Rings in Chemical and Biological Recognition

2003

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“…We have recently investigated 4Ј-alkylated oligonucleotide duplexes in term of their abilities to form duplexes and have found that complementary duplexes are formed, with few overall helix deviations in relation to their unmodified counterparts. [42] Nevertheless, the introduction of several modified residues into oligonucleotide duplexes did decrease the duplex stability of the respective oligonucleotides. Here we report on the effect of varying salt concentrations on duplex stability.…”

Section: Biophysical Properties Of Duplexes Containing 4ј-alkylated Omentioning

confidence: 99%

Substrates for Investigation of DNA Polymerase Function: Synthesis and Properties of 4′‐C‐Alkylated Oligonucleotides

2003

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In addition to their potential as diagnostic and therapeutic agents, modified oligonucleotides have also been shown to be highly valuable tools for examination of complex biological processes. Carefully designed nucleotide analogues have therefore found considerable application in investigations of DNA polymerase function and mechanism. To examine the contribution of primarily steric constraints on DNA polymerase selectivity, we have developed a new functional strategy based on the use of modified nucleotide analogues that differ primarily in their steric demand. Here we report the efficient synthesis of modified thymidine analogues bearing 4Ј-alkyl groups with varying steric demand, the effects of 4Ј-alkylation on sugar puckering, and the incorporation of

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“…This model has been substantiated by studies showing efficient incorporation of a large pyrene deoxynucleoside triphosphate in front of an abasic (AP) site by Escherichia coli polymerase I (Klenow fragment, KF) and T7 polymerase (11). Furthermore, C4′-alkyl-substituted dTTP analogues were used to show that increasing the size of the sugar ring also leads to steric exclusion (12–15). Polymerases in families A, B, X and RT have binding pockets that tightly accommodate a correct Watson–Crick base pair, supporting the notion that nucleotide selectivity for these enzymes largely depends on geometric selection for the shape and size of correct base pairs (16,17).…”

Section: Introductionmentioning

confidence: 99%

Incorporation of non-nucleoside triphosphate analogues opposite to an abasic site by human DNA polymerases and

Crespan

Zanoli

Khandazhinskaya

et al. 2005

Nucleic Acids Research

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A novel class of non-nucleoside triphosphate analogues, bearing hydrophobic groups sterically similar to nucleosides linked to the α-phosphate but lacking the chemical functional groups of nucleic acids, were tested against six different DNA polymerases (polymerases). Human polymerases α, β and λ, and Saccharomyces cerevisiae polymerase IV, were inhibited with different potencies by these analogues. On the contrary, Escherichia coli polymerase I and HIV-1 reverse transcriptase were not. Polymerase β incorporated these derivatives in a strictly Mn++-dependent manner. On the other hand, polymerase λ could incorporate some alkyltriphosphate derivatives with both Mg++ and Mn++, but only opposite to an abasic site on the template strand. The active site mutant polymerase λ Y505A showed an increased ability to incorporate the analogues. These results show for the first time that neither the base nor the sugar moieties of nucleotides are required for incorporation by family X DNA polymerases.

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DNA minor groove hydration probed with 4’-alkylated thymidines

Abstract: Employing modified oligonucleotides that are 4'-alkylated site-specifically we investigated the involvement of DNA minor groove hydration on DNA duplex stability and helix conformation.

Cited by 13 publications

References 19 publications

Interactions with Aromatic Rings in Chemical and Biological Recognition

Interactions with Aromatic Rings in Chemical and Biological Recognition

Substrates for Investigation of DNA Polymerase Function: Synthesis and Properties of 4′‐C‐Alkylated Oligonucleotides

Incorporation of non-nucleoside triphosphate analogues opposite to an abasic site by human DNA polymerases and

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