2'-O-[2-(methylthio)ethyl]-modified oligonucleotide: an analogue of 2'-O-[2-(methoxy)-ethyl]-modified oligonucleotide with improved protein binding properties and high binding affinity to target RNA.

Prakash TP, Manoharan M, Kawasaki AM, Fraser AS, Lesnik EA, Sioufi N, Leeds JM, Teplova M, Egli M
Biochemistry. 2002 41 (39): 11642-8

PMID: 12269806 · DOI:10.1021/bi020264t

A novel 2'-modification, 2'-O-[2-(methylthio)ethyl] or 2'-O-MTE, has been incorporated into oligonucleotides and evaluated for properties relevant to antisense activity. The results were compared with the previously characterized 2'-O-[2-(methoxy)ethyl] 2'-O-MOE modification. As expected, the 2'-O-MTE modified oligonucleotides exhibited improved binding to human serum albumin compared to the 2'-O-MOE modified oligonucleotides. The 2'-O-MTE oligonucleotides maintained high binding affinity to target RNA. Nuclease digestion of 2'-O-MTE oligonucleotides showed that they have limited resistance to exonuclease degradation. We analyzed the crystal structure of a decamer DNA duplex containing the 2'-O-MTE modifcation. Analysis of the crystal structure provides insight into the improved RNA binding affinity, protein binding affinity and limited resistance of 2'-O-MTE modified oligonucleotides to exonuclease degradation.

MeSH Terms (10)

Binding Sites Crystallography, X-Ray Nucleic Acid Heteroduplexes Nucleosides Oligodeoxyribonucleotides Oligodeoxyribonucleotides, Antisense Organophosphorus Compounds Protein Binding RNA Uridine

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