NMR solution structure of dsDNA containing a bicyclic D-arabino-configured nucleotide fixed in an O4'-endo sugar conformation

Henning V. Tømmerholt, Nanna K. Christensen, Poul Nielsen, Jesper Wengel, Paul C. Stein, Jens P. Jacobsen, Michael Petersen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

[3.2.0]bcANA is a D-arabino-configured bicyclic nucleotide with a 2′-O,3′-C-methylene bridge. We here present the high-resolution NMR structure of a [3.2.0]bcANA modified dsDNA nonamer with one modified nucleotide incorporated. NOE restraints were obtained by analysis of NOESY cross peak intensities using a full relaxation matrix approach, and subsequently these restraints were incorporated into a simulated annealing scheme for the structure determination. In addition, the furanose ring puckers of the deoxyribose moieties were determined by analysis of COSY cross peaks. The modified duplex adopts a B-like geometry with Watson–Crick base pairing in all base pairs and all glycosidic angles in the anti range. The stacking arrangement of the nucleobases appears to be unperturbed relative to the normal B-like arrangement. The 2′-O,3′-C-methylene bridge of the modified nucleotide is located at the brim of the major groove where it fits well into the B-type duplex framework. The sugar pucker of the [3.2.0]bcANA nucleotide is O4′-endo and this sugar conformation causes a change in the δ backbone angle relative to the C2′-endo deoxyribose sugar pucker. This change is absorbed locally by slight changes in the ε and ζ angles of the modified nucleotide. Overall, the [3.2.0]bcANA modifications fits very well into a B-like duplex framework and only small and local perturbations are observed relative to the unmodified dsDNA of identical base sequence.

Original languageEnglish
JournalOrganic & Biomolecular Chemistry
Volume2003
Issue number10
Pages (from-to)1790-1797
ISSN1477-0520
DOIs
Publication statusPublished - 2003

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Sugars
Conformations
Nucleotides
Nuclear magnetic resonance
Deoxyribose
Simulated annealing
Geometry

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@article{309085e0ba9a11dc9626000ea68e967b,
title = "NMR solution structure of dsDNA containing a bicyclic D-arabino-configured nucleotide fixed in an O4'-endo sugar conformation",
abstract = "[3.2.0]bcANA is a D-arabino-configured bicyclic nucleotide with a 2′-O,3′-C-methylene bridge. We here present the high-resolution NMR structure of a [3.2.0]bcANA modified dsDNA nonamer with one modified nucleotide incorporated. NOE restraints were obtained by analysis of NOESY cross peak intensities using a full relaxation matrix approach, and subsequently these restraints were incorporated into a simulated annealing scheme for the structure determination. In addition, the furanose ring puckers of the deoxyribose moieties were determined by analysis of COSY cross peaks. The modified duplex adopts a B-like geometry with Watson–Crick base pairing in all base pairs and all glycosidic angles in the anti range. The stacking arrangement of the nucleobases appears to be unperturbed relative to the normal B-like arrangement. The 2′-O,3′-C-methylene bridge of the modified nucleotide is located at the brim of the major groove where it fits well into the B-type duplex framework. The sugar pucker of the [3.2.0]bcANA nucleotide is O4′-endo and this sugar conformation causes a change in the δ backbone angle relative to the C2′-endo deoxyribose sugar pucker. This change is absorbed locally by slight changes in the ε and ζ angles of the modified nucleotide. Overall, the [3.2.0]bcANA modifications fits very well into a B-like duplex framework and only small and local perturbations are observed relative to the unmodified dsDNA of identical base sequence.",
author = "T{\o}mmerholt, {Henning V.} and Christensen, {Nanna K.} and Poul Nielsen and Jesper Wengel and Stein, {Paul C.} and Jacobsen, {Jens P.} and Michael Petersen",
year = "2003",
doi = "10.1039/B300848G",
language = "English",
volume = "2003",
pages = "1790--1797",
journal = "Organic & Biomolecular Chemistry",
issn = "1477-0520",
publisher = "Royal Society of Chemistry",
number = "10",

}

NMR solution structure of dsDNA containing a bicyclic D-arabino-configured nucleotide fixed in an O4'-endo sugar conformation. / Tømmerholt, Henning V.; Christensen, Nanna K.; Nielsen, Poul; Wengel, Jesper; Stein, Paul C.; Jacobsen, Jens P.; Petersen, Michael.

In: Organic & Biomolecular Chemistry, Vol. 2003, No. 10, 2003, p. 1790-1797.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - NMR solution structure of dsDNA containing a bicyclic D-arabino-configured nucleotide fixed in an O4'-endo sugar conformation

AU - Tømmerholt, Henning V.

AU - Christensen, Nanna K.

AU - Nielsen, Poul

AU - Wengel, Jesper

AU - Stein, Paul C.

AU - Jacobsen, Jens P.

AU - Petersen, Michael

PY - 2003

Y1 - 2003

N2 - [3.2.0]bcANA is a D-arabino-configured bicyclic nucleotide with a 2′-O,3′-C-methylene bridge. We here present the high-resolution NMR structure of a [3.2.0]bcANA modified dsDNA nonamer with one modified nucleotide incorporated. NOE restraints were obtained by analysis of NOESY cross peak intensities using a full relaxation matrix approach, and subsequently these restraints were incorporated into a simulated annealing scheme for the structure determination. In addition, the furanose ring puckers of the deoxyribose moieties were determined by analysis of COSY cross peaks. The modified duplex adopts a B-like geometry with Watson–Crick base pairing in all base pairs and all glycosidic angles in the anti range. The stacking arrangement of the nucleobases appears to be unperturbed relative to the normal B-like arrangement. The 2′-O,3′-C-methylene bridge of the modified nucleotide is located at the brim of the major groove where it fits well into the B-type duplex framework. The sugar pucker of the [3.2.0]bcANA nucleotide is O4′-endo and this sugar conformation causes a change in the δ backbone angle relative to the C2′-endo deoxyribose sugar pucker. This change is absorbed locally by slight changes in the ε and ζ angles of the modified nucleotide. Overall, the [3.2.0]bcANA modifications fits very well into a B-like duplex framework and only small and local perturbations are observed relative to the unmodified dsDNA of identical base sequence.

AB - [3.2.0]bcANA is a D-arabino-configured bicyclic nucleotide with a 2′-O,3′-C-methylene bridge. We here present the high-resolution NMR structure of a [3.2.0]bcANA modified dsDNA nonamer with one modified nucleotide incorporated. NOE restraints were obtained by analysis of NOESY cross peak intensities using a full relaxation matrix approach, and subsequently these restraints were incorporated into a simulated annealing scheme for the structure determination. In addition, the furanose ring puckers of the deoxyribose moieties were determined by analysis of COSY cross peaks. The modified duplex adopts a B-like geometry with Watson–Crick base pairing in all base pairs and all glycosidic angles in the anti range. The stacking arrangement of the nucleobases appears to be unperturbed relative to the normal B-like arrangement. The 2′-O,3′-C-methylene bridge of the modified nucleotide is located at the brim of the major groove where it fits well into the B-type duplex framework. The sugar pucker of the [3.2.0]bcANA nucleotide is O4′-endo and this sugar conformation causes a change in the δ backbone angle relative to the C2′-endo deoxyribose sugar pucker. This change is absorbed locally by slight changes in the ε and ζ angles of the modified nucleotide. Overall, the [3.2.0]bcANA modifications fits very well into a B-like duplex framework and only small and local perturbations are observed relative to the unmodified dsDNA of identical base sequence.

U2 - 10.1039/B300848G

DO - 10.1039/B300848G

M3 - Journal article

VL - 2003

SP - 1790

EP - 1797

JO - Organic & Biomolecular Chemistry

JF - Organic & Biomolecular Chemistry

SN - 1477-0520

IS - 10

ER -