1AC3

SOLUTION STRUCTURE OF AN RNA-DNA HYBRID DUPLEX CONTAINING A 3'-THIOFORMACETAL LINKER AND AN RNA A-TRACT, NMR, 8 STRUCTURES

Summary for 1AC3

• Entry DOI: 10.2210/pdb1ac3/pdb
• Descriptor: ANTISENSE HYBRID DUPLEX, DNA (5'-D(*(TCP)P*TP*GP*CP*GP*C)-3') (2 entities in total)
• Functional Keywords: rna, dna, antisense oligonucleotides, thioformacetal backbone modification, hybrid duplex, dna-rna hybrid complex, dna-rna hybrid
• Total number of polymer chains: 2
• Total formula weight: 7468.89

Authors

Cross, C.W.,Rice, J.S.,Gao, X. (deposition date: 1997-02-11, release date: 1997-06-16, Last modification date: 2024-04-10)

Primary citation

Cross, C.W.,Rice, J.S.,Gao, X.
Solution structure of an RNA x DNA hybrid duplex containing a 3'-thioformacetal linker and an RNA A-tract.
Biochemistry, 36:4096-4107, 1997

PubMed 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.

PubMed: 9100003
DOI: 10.1021/bi962382k

Experimental method

SOLUTION NMR