Stability of Stereoregular Oligo(nucleoside Phosphorothioate)s in Human Plasma: Diastereoselectivity of Plasma 3‵-Exonuclease
- 1 February 1997
- journal article
- research article
- Published by Mary Ann Liebert Inc in Antisense and Nucleic Acid Drug Development
- Vol. 7 (1) , 43-48
- https://doi.org/10.1089/oli.1.1997.7.43
Abstract
The stability of stereoregular oligo(nucleoside phosphorothioate)s (PS-oligos) in human plasma has been studied. 3‵-Exonuclease present in human plasma appeared to be RP specific, that is, it cleaves internucleotide phosphorothioate linkages of [RP]-configuration and not those of [SP]-configuration. Therefore, PS-oligos containing all phosphorothioate internucleotide linkages of [RP]-configuration [RP-PS-oligos]) are more effectively degraded by the enzyme than PS-oligos prepared via nonstereocontrolled methods (so-called random mixture of diastereomers [Mix-PS-oligos]), whereas oligo(nucleoside phosphorothioate)s of [SP]-configuration remain intact. The enzyme activity depends on the sequence of nucleobases. The presence of deoxycytidine units (three or more residues) at the 3‵-end of PS-oligo substrate significantly inhibits the enzyme activity.Keywords
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