Activation of human RNase L by 2'- and 5'-O-methylphosphonate-modified oligoadenylates
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
22169265
DOI
10.1016/j.bmcl.2011.11.040
PII: S0960-894X(11)01584-8
Knihovny.cz E-resources
- MeSH
- Adenine Nucleotides chemistry MeSH
- Cell-Free System MeSH
- Time Factors MeSH
- Models, Chemical MeSH
- Dimerization MeSH
- Endoribonucleases chemistry MeSH
- Chemistry, Pharmaceutical methods MeSH
- Humans MeSH
- Mice MeSH
- Oligoribonucleotides chemistry MeSH
- Organophosphonates chemistry MeSH
- Drug Design MeSH
- Fluorescence Resonance Energy Transfer methods MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 2-5A-dependent ribonuclease MeSH Browser
- 2',5'-oligoadenylate MeSH Browser
- Adenine Nucleotides MeSH
- Endoribonucleases MeSH
- Oligoribonucleotides MeSH
- Organophosphonates MeSH
To determine the influence of internucleotide linkage and sugar ring conformation, and the role of 5'-terminal phosphate, on the activation of human RNase L, a series of 2'- and 5'-O-methylphosphonate-modified tetramers were synthesized from appropriate monomeric units and evaluated for their ability to activate human RNase L. Tetramers pAAAp(c)X modified by ribo, arabino or xylo 5'-phosphonate unit p(c)X activated RNase L with efficiency comparable to that of natural activator. Moreover, incorporation of phosphonate linkages ensured the stability against cleavage by nucleases. The substitution of 5'-terminal phosphate for 5'-terminal phosphonate in tetramer p(c)XAAA afforded tetramers with excellent activation efficiency and with complete stability against cleavage by phosphomonoesterases.
References provided by Crossref.org
Recognition of 2',5'-linked oligoadenylates by human ribonuclease L: molecular dynamics study
