Nature Structural Biology
5, 271 - 276 (1998)
doi:10.1038/nsb0498-271
Structure of a stereoregular phosphorothioate DNA/RNA duplexM. Bachelin1, 4, G. Hessler1, 4, G. Kurz1, 2, 4, J. G. Hacia3, P. B. Dervan3
& H. Kessler1, 5
1Institut für Organische Chemie und Biochemie, TU München, Lichtenbergstr. 4, D-85747 Garching, Germany.
2Present address: Laboratoire de Chimie Supramoléculaire, Université Louis Pasteur, 4 rue Blaise Pascal, 67000 Strasbourg, France.
3Division of Chemistry and Chemical Engineering and The Beckman Institute, California Institute of Technology, Pasadena, California 91125, USA.
4These authors contributed equally to this work.
5email: kessler@artus.org.chemie.tu-muenchen.de In this work, we present the first NMR solution structure of a DNA/RNA hybrid containing stereoregular R
P-phosphorothioate modifications of all DNA backbone linkages. The complex of the enzymatically synthesized phosphorothioate DNA octamer (all-R
P)-d(GCGTCAGG) and its complementary RNA r(CCUGACGC) was found to adopt an overall conformation within the A-form family. Most helical parameters and the sugar puckers of the DNA strand assume values intermediate between A- and B-form. The close structural similarity with the unmodified DNA/RNA hybrid of the same sequence may explain why both the natural and the sulfur-substituted complex can be recognized and digested by ribonuclease H.
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