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ID: ALA2057064

Journal: Bioorg Med Chem Lett

Title: Activation of human RNase L by 2'- and 5'-O-methylphosphonate-modified oligoadenylates.

Authors: Páv O, Panova N, Snášel J, Zborníková E, Rosenberg I.

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.

CiteXplore: 22169265

DOI: 10.1016/j.bmcl.2011.11.040