1cx5

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ANTISENSE DNA/RNA HYBRID CONTAINING MODIFIED BACKBONE

Overview

The solution structure of an antisense DNA.RNA hybrid duplex, d(CGCGTT-MMI-TTGCGC).r(GCGCAAAACGCG) (designated R4), containing an MMI, backbone linker [3'-CH(2)N(CH(3))-O5'], is elucidated. The structural, details of the MMI linker, its structural effects on the neighboring, residues, and the molecular basis of the MMI effects are examined. The, lipophilic N-methyl group of MMI is peripheral to the helix, assuming a, conformation that is most stable with regard to the N-O torsion angle. The, MMI linker promotes a 3'-endo conformation for the sugar moieties at both, 3'- and 5'-adjacent positions and a backbone kink involving distant, residues along the 3'-direction. Comparison of R4 with other analogous, hybrid duplexes previously studied in this laboratory reveals a new family, of low-energy helical conformations that can be accommodated in stable, duplexes and a common feature of C3'-modified sugars for adopting a, C3'-endo pucker. The results of these studies emphasize the interplay of, several factors that govern the formation of stable hybrid duplexes and, provide a basis for the understanding of the biological role of the MMI, modifications, which are important building blocks for a family of, promising chimeric antisense oligonucleotides.

About this Structure

1CX5 is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.

Reference

NMR structure of an antisense DNA.RNA hybrid duplex containing a 3'-CH(2)N(CH(3))-O-5' or an MMI backbone linker., Yang X, Han X, Cross C, Bare S, Sanghvi Y, Gao X, Biochemistry. 1999 Sep 28;38(39):12586-96. PMID:10504227

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