PDBsum entry 1ac3

DNA-RNA hybrid

PDB id: 1ac3

Contents

DNA/RNA

PDB id:

1ac3

Name:

DNA-RNA hybrid

Title:

Solution structure of an RNA-DNA hybrid duplex containing a 3'- thioformacetal linker and an RNA a-tract, nmr, 8 structures

Structure:

Antisense hybrid duplex. Chain: a. Engineered: yes. Other_details: t6-3'-thioformacetal in the DNA strand. DNA (5'-d( (Tcp)p Tp Gp Cp Gp C)-3'). Chain: b. Engineered: yes. Other_details: t6-3'-thioformacetal in the DNA strand

Source:

Synthetic: yes. Synthetic: yes

NMR struc:

8 models

Authors:

C.W.Cross,J.S.Rice,X.Gao

Key ref:

C.W.Cross et al. (1997). Solution structure of an RNA x DNA hybrid duplex containing a 3'-thioformacetal linker and an RNA A-tract. Biochemistry, 36, 4096-4107. PubMed id: 9100003 DOI: 10.1021/bi962382k

Date:

11-Feb-97 Release date: 16-Jun-97

DNA/RNA chains

C-G-C-G-T-TSP-TCP-T-G-C-G-C 12 bases

G-C-G-C-A-A-A-A-C-G-C-G 12 bases

DOI no: 10.1021/bi962382k

Biochemistry 36:4096-4107 (1997)

PubMed id: 9100003

Solution structure of an RNA x DNA hybrid duplex containing a 3'-thioformacetal linker and an RNA A-tract.

C.W.Cross, J.S.Rice, X.Gao.

ABSTRACT

Neutral and achiral backbone linkers are promising replacements for the phosphodiester linkages of antisense oligonucleotides that target mRNA sequences. Results are presented here for the solution structure elucidation by NMR of an RNA x DNA hybrid duplex, r(GCGCAAAACGCG) x d(CGCGTT-SCH2O-TTGCGC) (designated RIII), containing a 3'-thioformacetal (3'-TFMA) backbone substitution in the DNA strand. The 3'-thioformacetal linker can be accommodated in the hybrid duplex in a conformation that is drastically different from its form in a DNA x DNA duplex but close to that of the canonical A-form helix, reflecting the sequence requirement for hybridization. While the global features of RIII are similar to what are described in the literature, the 3'-TFMA modification drives sugar puckers of the adjacent residues to more C3'-endo-like conformations and causes distortions in related twist angles and helical rises. The helical conformation analyses of each of the two strands and the hybrid duplex enable a clear account of the conformational variability of both the DNA and RNA strands. The A-tract in the RNA strand features an overall straight helix and a more prominent bend at the 3'-end CG step. The structure of RIII provides a structural basis for the improved thermal stability of RIII compared to the corresponding DNA x DNA duplex and insights into the factors that are important concerns for the design of new, effective antisense oligonucleotides.