2M39

The solution structure of 3',5'-LINKED 2'-O-(2-METHOXYETHYL)-RNA DUPLEX

Summary for 2M39

• Entry DOI: 10.2210/pdb2m39/pdb
• NMR Information: BMRB: 18950
• Descriptor: RNA (5'-R(*(C5L)P*(G48)P*(C5L)P*(G48)P*(A44)P*(A44)P*(T39)P*(T39)P*(C5L)P*(G48)P*(C5L)P*DG)-3') (1 entity in total)
• Functional Keywords: duplex, (3', 5')-rna, 2'-o-(2-methoxyethyl) ribose, rna
• Biological source: Synthetic
• Total number of polymer chains: 2
• Total formula weight: 9068.73

Authors

Plevnik, M.,Cevec, M.,Plavec, J. (deposition date: 2013-01-15, release date: 2013-11-27, Last modification date: 2024-05-15)

Primary citation

Plevnik, M.,Cevec, M.,Plavec, J.
NMR structure of 2'-O-(2-methoxyethyl) modified and C5-methylated RNA dodecamer duplex.
Biochimie, 95:2385-2391, 2013

PubMed Abstract: The solution-state structure of 2'-O-(2-methoxyethly) substituted dodecamer r(*CG*CGAA*U*U*CG*C)d(G), 2'-MOE RNA, with all cytosines and uracils methylated at the C5-position has been determined by NMR spectroscopy. The chemical modifications were used to improve the oligonucleotide's drug-like properties. The 2'-MOE group drives pseudorotational equilibrium of the ribofuranose moiety to the N-type conformation and supposedly results in structural preorganization leading to high affinity of a modified oligonucleotide towards its complementary biological target, improved pharmacokinetic and toxicological properties. The high melting temperature of the antiparallel duplex structure adopted by 2'-MOE RNA was explained through the formation of a stable A-form RNA consistent with effective base-pairing and stacking interactions. The comparison of the solution-state structure with the crystal structure of a non-methylated analogue shows an increase in the stacking at the base pair steps for the C5-methylated 2'-MOE RNA duplex. The MOE substituents adopt a well-defined structure in the minor groove with the predominant gauche conformations around the ethylene bond.

PubMed: 24012551
DOI: 10.1016/j.biochi.2013.08.025

Experimental method

SOLUTION NMR