1CX5

ANTISENSE DNA/RNA HYBRID CONTAINING MODIFIED BACKBONE

Summary for 1CX5

• Entry DOI: 10.2210/pdb1cx5/pdb
• Descriptor: 5'-D(*CP*GP*CP*GP*TP*T*(MMT)P*TP*GP*CP*GP*C), 5'-R(*GP*CP*GP*CP*AP*AP*AP*AP*CP*GP*CP*G) (2 entities in total)
• Functional Keywords: antisense, dna/rna hybrid, modified backbone linker, dna-rna hybrid
• Total number of polymer chains: 2
• Total formula weight: 7481.87

Authors

Yang, X.,Han, X.,Cross, C.,Sanghvi, Y.,Gao, X. (deposition date: 1999-08-28, release date: 1999-09-14, Last modification date: 2024-05-22)

Primary citation

Yang, X.,Han, X.,Cross, C.,Bare, S.,Sanghvi, Y.,Gao, X.
NMR structure of an antisense DNA.RNA hybrid duplex containing a 3'-CH(2)N(CH(3))-O-5' or an MMI backbone linker.
Biochemistry, 38:12586-12596, 1999

PubMed Abstract: 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.

PubMed: 10504227
DOI: 10.1021/bi990456x

Experimental method

SOLUTION NMR