NMR structure of 2'-O-(2-methoxyethyl) modified and C5-methylated RNA dodecamer duplex
| Autor: | Miha Plevnik, Mirko Cevec, Janez Plavec |
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| Rok vydání: | 2013 |
| Předmět: |
Oligoribonucleotides
Base pair Stereochemistry Chemistry Oligonucleotide Stacking RNA General Medicine Nuclear magnetic resonance spectroscopy Antiparallel (biochemistry) Biochemistry Dodecameric protein Duplex (building) Nucleic Acid Conformation Base Pairing Nuclear Magnetic Resonance Biomolecular |
| Zdroj: | Biochimie. 95(12) |
| ISSN: | 1638-6183 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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