title: Stability of stereoregular oligo(nucleoside phosphorothioate)s in human plasma: diastereoselectivity of plasma 3'-exonuclease.
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 nonstereo-controlled methods (so-called random mixture of diastereomers [Mix-PS-oligos]), whereas oligo(nucleoside phosphorothioate)s of [S(P)]-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.
authors.affiliation: Polish Academy of Sciences, Department of Bioorganic Chemistry, Lódź, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Koziołkiewicz
authors.forename: M
authors.initials: M
authors.lastname: Wójcik
authors.forename: A
authors.initials: A
authors.lastname: Kobylańska
authors.forename: B
authors.initials: B
authors.lastname: Karwowski
authors.forename: B
authors.initials: B
authors.lastname: Rebowska
authors.forename: P
authors.initials: P
authors.lastname: Guga
authors.forename: W J
authors.initials: WJ
authors.lastname: Stec
mesh_terms: D004355:Drug Stability; D004591:Electrophoresis, Polyacrylamide Gel; D005090:Exodeoxyribonucleases / Q000037:antagonists & inhibitors / Q000097:blood* / Q000378:metabolism; D006801:Humans; D009690:Nucleic Acid Conformation; D013237:Stereoisomerism; D013873:Thionucleotides / Q000097:blood* / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D013873:Thionucleotides; D005090:Exodeoxyribonucleases