1MLX

Crystal Structure Analysis of a 2'-O-[2-(Methylthio)-ethyl]-Modified Oligodeoxynucleotide Duplex

1MLX の概要

• エントリーDOI: 10.2210/pdb1mlx/pdb
• 分子名称: 5'-D(*GP*CP*GP*TP*AP*SMTP*AP*CP*GP*C)-3' (2 entities in total)
• 機能のキーワード: dna, double helix, a-form, antisense modification, nucleic acid analogue, rna affinity, nuclease resistance, protein binding affinity, high resolution structure, hydration
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 6270.30

構造登録者

Prakash, T.P.,Manoharan, M.,Kawasaki, A.M.,Fraser, A.S.,Lesnik, E.A.,Sioufi, N.,Leeds, J.M.,Teplova, M.,Egli, M. (登録日: 2002-08-31, 公開日: 2002-12-04, 最終更新日: 2024-02-14)

主引用文献

Prakash, T.P.,Manoharan, M.,Kawasaki, A.M.,Fraser, A.S.,Lesnik, E.A.,Sioufi, N.,Leeds, J.M.,Teplova, M.,Egli, M.
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
Biochemistry, 41:11642-11648, 2002

PubMed Abstract: 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.

PubMed: 12269806
DOI: 10.1021/bi020264t

実験手法

X-RAY DIFFRACTION (1.25 Å)