title: Activation of human RNase L by 2'- and 5'-O-methylphosphonate-modified oligoadenylates.
abstract: 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.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo n. 2, 166 10 Prague 6, Czech Republic.
authors.forename: Ondřej
authors.initials: O
authors.lastname: Páv
authors.forename: Natalya
authors.initials: N
authors.lastname: Panova
authors.forename: Jan
authors.initials: J
authors.lastname: Snášel
authors.forename: Eva
authors.initials: E
authors.lastname: Zborníková
authors.forename: Ivan
authors.initials: I
authors.lastname: Rosenberg
mesh_terms: D000227:Adenine Nucleotides / Q000737:chemistry*; D000818:Animals; D002474:Cell-Free System; D002626:Chemistry, Pharmaceutical / Q000379:methods; D019281:Dimerization; D015195:Drug Design; D004722:Endoribonucleases / Q000737:chemistry*; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods; D006801:Humans; D051379:Mice; D008956:Models, Chemical; D009843:Oligoribonucleotides / Q000737:chemistry*; D063065:Organophosphonates / Q000737:chemistry*; D013997:Time Factors
chemical_list: D000227:Adenine Nucleotides; D009843:Oligoribonucleotides; D063065:Organophosphonates; C023505:2',5'-oligoadenylate; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease