2m39

Publication Abstract from PubMed

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.

NMR structure of 2'-O-(2-methoxyethyl) modified and C5-methylated RNA dodecamer duplex.,Plevnik M, Cevec M, Plavec J Biochimie. 2013 Dec;95(12):2385-91. doi: 10.1016/j.biochi.2013.08.025. Epub 2013 , Sep 3. PMID:24012551^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.