The Crystal Structure Analysis of D(CGCGAASSCGCG)2, a Synthetic DNA Dodecamer Duplex Containing Four 4'-thio-2'-deoxythymidine Nucleotides

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 1996 Mar 1

PMID 8600465

Citations 7

Authors

T J Boggon

E L Hancox

B A Connolly

W N Hunter

T Brown

R T Walker

G A Leonard

Affiliations

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Abstract

The crystal structure refinement of the synthetic dodecamer d(CGCGAASSCGCG), where S = 4'-thio-2'-deoxythymidine, has converged at R=0.201 for 2605 reflections with F > 2sigma(F) in the resolution range 8.0-2.4 A for a model consisting of the dodecamer duplex and 66 water molecules. A comparison of its structure with that of the native dodecamer d(CGCGAATTCGCG) has revealed that the major differences between the two structures is a change in the conformation of the sugar-phosphate backbone in the regions at and adjacent to the positions of the modified nucleosides. Examination of the fine structural parameters for each of the structures reveals that the thiosugars adopt a C3'-exo conformation in d(CGCGAASSCGCG), rather than the approximate C1'-exo conformation found for the analogous sugars in the structure of d(CGCGAATTCGCG). The observed differences in structure between the two duplexes may help to explain the enhanced resistance to nuclease digestion of synthetic oligonucleotides containing 4'-thio-2'-deoxynucleotides.

Citing Articles

Crystallographic studies of chemically modified nucleic acids: a backward glance.

Egli M, Pallan P Chem Biodivers. 2010; 7(1):60-89.

PMID: 20087997 PMC: 2905155. DOI: 10.1002/cbdv.200900177.

Unexpected A-form formation of 4'-thioDNA in solution, revealed by NMR, and the implications as to the mechanism of nuclease resistance.

Matsugami A, Ohyama T, Inada M, Inoue N, Minakawa N, Matsuda A Nucleic Acids Res. 2008; 36(6):1805-12.

PMID: 18252770 PMC: 2330235. DOI: 10.1093/nar/gkn011.

Influence of the incorporation of a cyclohexenyl nucleic acid (CeNA) residue onto the sequence d(CGCGAATTCGCG).

Robeyns K, Herdewijn P, Meervelt L Nucleic Acids Res. 2007; 36(5):1407-14.

PMID: 18160414 PMC: 2275148. DOI: 10.1093/nar/gkm1132.

Synthesis and properties of 4'-ThioDNA: unexpected RNA-like behavior of 4'-ThioDNA.

Inoue N, Minakawa N, Matsuda A Nucleic Acids Res. 2006; 34(12):3476-83.

PMID: 16855286 PMC: 1524900. DOI: 10.1093/nar/gkl491.

Syntheses of 4'-thioribonucleosides and thermodynamic stability and crystal structure of RNA oligomers with incorporated 4'-thiocytosine.

Haeberli P, Berger I, Pallan P, Egli M Nucleic Acids Res. 2005; 33(13):3965-75.

PMID: 16027443 PMC: 1178003. DOI: 10.1093/nar/gki704.

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