Stability of stereoregular oligo(nucleoside phosphorothioate)s in human plasma: diastereoselectivity of plasma 3'-exonuclease.
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.
Koziołkiewicz
M
M
Polish Academy of Sciences, Department of Bioorganic Chemistry, Lódź, Poland.
Wójcik
M
M
Kobylańska
A
A
Karwowski
B
B
Rebowska
B
B
Guga
P
P
Stec
W J
WJ
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
D013873:Thionucleotides; D005090:Exodeoxyribonucleases