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Biochemistry
2009 Dec 22;4850:11994-2004. doi: 10.1021/bi9014133.
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Impact of sugar pucker on base pair and mispair stability.
Williams AA
,
Darwanto A
,
Theruvathu JA
,
Burdzy A
,
Neidigh JW
,
Sowers LC
.
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The selection of nucleoside triphosphates by a polymerase is controlled by several energetic and structural features, including base pairing geometry as well as sugar structure and conformation. Whereas base pairing has been considered exhaustively, substantially less is known about the role of sugar modifications for both nucleotide incorporation and primer extension. In this study, we synthesized oligonucleotides containing 2'-fluoro-modified nucleosides with constrained sugar pucker in an internucleotide position and, for the first time, at a primer 3'-end. The thermodynamic stability of these duplexes was examined. The nucleoside 2'-deoxy-2'-fluoroarabinofuranosyluracil [U(2'F(ara))] favors the 2'-endo conformation (DNA-like), while 2'-deoxy-2'-fluororibofuranosyluracil [U(2'F(ribo))] favors the 3'-endo conformation (RNA-like). Oligonucleotides containing U(2'F(ara)) have slightly higher melting temperatures (T(m)) than those containing U(2'F(ribo)) when located in internucleotide positions or at the 3'-end and when correctly paired with adenine or mispaired with guanine. However, both modifications decrease the magnitude of DeltaH degrees and DeltaS degrees for duplex formation in all sequence contexts. In examining the thermodynamic properties for this set of oligonucleotides, we find entropy-enthalpy compensation is apparent. Our thermodynamic findings led to a series of experiments with DNA ligase that reveal, contrary to expectation based upon observed T(m) values, that the duplex containing the U(2'F(ribo)) analogue is more easily ligated. The 2'-fluoro-2'-deoxynucleosides examined here are valuable probes of the impact of sugar constraint and are also members of an important class of antitumor and antiviral agents. The data reported here may facilitate an understanding of the biological properties of these agents, as well as the contribution of sugar conformation to replication fidelity.
Aboul-ela,
Base-base mismatches. Thermodynamics of double helix formation for dCA3XA3G + dCT3YT3G (X, Y = A,C,G,T).
1985, Pubmed
Aboul-ela,
Base-base mismatches. Thermodynamics of double helix formation for dCA3XA3G + dCT3YT3G (X, Y = A,C,G,T).
1985,
Pubmed
Allawi,
Thermodynamics and NMR of internal G.T mismatches in DNA.
1997,
Pubmed
Allawi,
NMR solution structure of a DNA dodecamer containing single G.T mismatches.
1998,
Pubmed
Altona,
Conformational analysis of the sugar ring in nucleosides and nucleotides. A new description using the concept of pseudorotation.
1972,
Pubmed
Astatke,
How E. coli DNA polymerase I (Klenow fragment) distinguishes between deoxy- and dideoxynucleotides.
1998,
Pubmed
Beard,
Structural insights into the origins of DNA polymerase fidelity.
2003,
Pubmed
Berger,
Crystal structures of B-DNA with incorporated 2'-deoxy-2'-fluoro-arabino-furanosyl thymines: implications of conformational preorganization for duplex stability.
1998,
Pubmed
Boulard,
The pH dependent configurations of the C.A mispair in DNA.
1992,
Pubmed
Carbonnaux,
An NMR structural study of deaminated base pairs in DNA.
1990,
Pubmed
Connolly,
Synthesis and properties of oligonucleotides containing 4-thiothymidine, 5-methyl-2-pyrimidinone-1-beta-D(2'-deoxyriboside) and 2-thiothymidine.
1989,
Pubmed
Cui,
Characterization of synthetic oligonucleotides containing biologically important modified bases by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
2008,
Pubmed
Cullinan,
Solution structure of a DNA duplex containing the exocyclic lesion 3,N4-etheno-2'-deoxycytidine opposite 2'-deoxyguanosine.
1997,
Pubmed
Delort,
Influence of uracil defect on DNA structure: 1H NMR investigation at 500 MHz.
1985,
Pubmed
Ferrin,
Nuclear Overhauser effect studies of the conformations and binding site environments of deoxynucleoside triphosphate substrates bound to DNA polymerase I and its large fragment.
1985,
Pubmed
Goodman,
DNA polymerase fidelity: from genetics toward a biochemical understanding.
1998,
Pubmed
Ikeda,
The effect of two antipodal fluorine-induced sugar puckers on the conformation and stability of the Dickerson-Drew dodecamer duplex [d(CGCGAATTCGCG)]2.
1998,
Pubmed
Johnson,
Conformational coupling in DNA polymerase fidelity.
1993,
Pubmed
Joyce,
Reactions at the polymerase active site that contribute to the fidelity of Escherichia coli DNA polymerase I (Klenow fragment).
1992,
Pubmed
Joyce,
DNA polymerase fidelity: kinetics, structure, and checkpoints.
2004,
Pubmed
Kalota,
2'-deoxy-2'-fluoro-beta-D-arabinonucleic acid (2'F-ANA) modified oligonucleotides (ON) effect highly efficient, and persistent, gene silencing.
2006,
Pubmed
Kuchta,
Inhibition of DNA primase and polymerase alpha by arabinofuranosylnucleoside triphosphates and related compounds.
1992,
Pubmed
Lewis,
Mammalian DNA polymerases alpha, beta, gamma, delta, and epsilon incorporate fialuridine (FIAU) monophosphate into DNA and are inhibited competitively by FIAU Triphosphate.
1994,
Pubmed
Liu,
DNA ligases ensure fidelity by interrogating minor groove contacts.
2004,
Pubmed
Marquez,
Experimental and structural evidence that herpes 1 kinase and cellular DNA polymerase(s) discriminate on the basis of sugar pucker.
2004,
Pubmed
Martin,
Synthesis and antiviral activity of monofluoro and difluoro analogues of pyrimidine deoxyribonucleosides against human immunodeficiency virus (HIV-1).
1990,
Pubmed
McTigue,
Sequence-dependent thermodynamic parameters for locked nucleic acid (LNA)-DNA duplex formation.
2004,
Pubmed
Mendelman,
Base mispair extension kinetics. Comparison of DNA polymerase alpha and reverse transcriptase.
1990,
Pubmed
Mikita,
Functional consequences of the arabinosylcytosine structural lesion in DNA.
1988,
Pubmed
Ono,
2'-Fluoro modified nucleic acids: polymerase-directed synthesis, properties and stability to analysis by matrix-assisted laser desorption/ionization mass spectrometry.
1997,
Pubmed
Peng,
G-quadruplex induced stabilization by 2'-deoxy-2'-fluoro-D-arabinonucleic acids (2'F-ANA).
2007,
Pubmed
Perrino,
Incorporation of cytosine arabinoside monophosphate into DNA at internucleotide linkages by human DNA polymerase alpha.
1992,
Pubmed
Perrino,
Exonucleases and the incorporation of aranucleotides into DNA.
1999,
Pubmed
Perrino,
Extension of mismatched 3' termini of DNA is a major determinant of the infidelity of human immunodeficiency virus type 1 reverse transcriptase.
1989,
Pubmed
Petruska,
Comparison of nucleotide interactions in water, proteins, and vacuum: model for DNA polymerase fidelity.
1986,
Pubmed
Petruska,
Comparison between DNA melting thermodynamics and DNA polymerase fidelity.
1988,
Pubmed
Pinto,
2'-Deoxy-2'-fluorouridine-5'-triphosphates: a possible substrate for E. coli RNA polymerase.
1979,
Pubmed
Pon,
Hydroquinone-O,O'-diacetic acid ('Q-linker') as a replacement for succinyl and oxalyl linker arms in solid phase oligonucleotide synthesis.
1997,
Pubmed
Puglisi,
Absorbance melting curves of RNA.
1989,
Pubmed
Richardson,
Polymerization of the triphosphates of AraC, 2',2'-difluorodeoxycytidine (dFdC) and OSI-7836 (T-araC) by human DNA polymerase alpha and DNA primase.
2004,
Pubmed
Richardson,
Polymerization of 2'-fluoro- and 2'-O-methyl-dNTPs by human DNA polymerase alpha, polymerase gamma, and primase.
2000,
Pubmed
SantaLucia,
Improved nearest-neighbor parameters for predicting DNA duplex stability.
1996,
Pubmed
Shah,
Variants of DNA polymerase Beta extend mispaired DNA due to increased affinity for nucleotide substrate.
2003,
Pubmed
Sowers,
Base stacking and molecular polarizability: effect of a methyl group in the 5-position of pyrimidines.
1987,
Pubmed
Thompson,
Interactions of calf thymus DNA polymerase alpha with primer/templates.
1995,
Pubmed
Tonelli,
Insights into the dynamic nature of DNA duplex structure via analysis of nuclear Overhauser effect intensities.
1998,
Pubmed
Trempe,
NMR solution structure of an oligonucleotide hairpin with a 2'F-ANA/RNA stem: implications for RNase H specificity toward DNA/RNA hybrid duplexes.
2001,
Pubmed
Vaidyanathan,
Preparation of 5-[131I]iodo- and 5-[211At]astato-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) uracil by a halodestannylation reaction.
1998,
Pubmed
Wilds,
Duplex recognition by oligonucleotides containing 2'-deoxy-2'-fluoro-D-arabinose and 2'-deoxy-2'-fluoro-D-ribose. Intermolecular 2'-OH-phosphate contacts versus sugar puckering in the stabilization of triple-helical complexes.
1999,
Pubmed
Wilds,
2'-Deoxy-2'-fluoro-beta-D-arabinonucleosides and oligonucleotides (2'F-ANA): synthesis and physicochemical studies.
2000,
Pubmed
Ziemkowski,
Interactions of 2'-fluoro-substituted dUMP analogues with thymidylate synthase.
2007,
Pubmed
Zinnen,
Misincorporation and mispaired primer extension by human immunodeficiency virus reverse transcriptase.
1994,
Pubmed
