Abstract
Phosphorodithioate (PS2) oligodeoxynucleotides (oligos) represent a relatively new class of backbone-modified oligo that have potential use as antisense agents. PS2 oligos are isoelectronic with phosphodiester (PO) and phosphoromonothioate (PS) oligos, and are nuclease resistant. However, unlike their PS congeners, PS2 oligos do not contain chiral centers. Little is known about the manner in which PS2 oligos interact with biological systems. In this study, we compare the cellular pharmacology of PS and PS2 oligos in HL60 cells. Cell surface binding, internalization, and compartmentalization are examined. Furthermore, the ability of PS and PS2 oligos to bind to rsCD4 and bFGF and to inhibit the activity of protein kinase C (PKC) is examined. Although the behavior of PS2 oligos closely parallels that of PS oligos, PS2 oligos appear to interact with some biological systems in a slightly different manner than PS oligos. These results indicate that PS2 oligos may have therapeutic potential other than as antisense agents.
References
Jul 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·S Ohkuma, B Poole
Jul 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·W S MarshallM H Caruthers
Nov 11, 1991·Nucleic Acids Research·W J StecB Uznanski
Feb 15, 1990·The Biochemical Journal·S A RotenbergI B Weinstein
Feb 7, 1989·Biochemistry·C MajumdarS H Wilson
Jun 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·M MatsukuraS Broder
Dec 1, 1989·AIDS Research and Human Retroviruses·C A SteinJ S Cohen
Sep 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·L A YakubovV V Vlassov
May 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·S L LokeL M Neckers
Apr 25, 1988·Nucleic Acids Research·C A SteinJ S Cohen
Nov 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·E J BowmanK Altendorf
Apr 1, 1987·Journal of Cellular Physiology·D Moscatelli
Jan 1, 1985·Advances in Enzyme Regulation·D G KnorreG G Karpova
Dec 1, 1973·Biochemical Pharmacology·Y Cheng, W H Prusoff
Mar 12, 1993·Science·W S Marshall, M H Caruthers
Oct 11, 1994·Nucleic Acids Research·J L Tonkinson, C A Stein
Dec 11, 1993·Nucleic Acids Research·M K GhoshJ S Cohen
Aug 20, 1993·Science·C A Stein, Y C Cheng
May 11, 1993·Biochemistry·C A SteinS A Rotenberg
Citations
Aug 28, 2016·Nucleic Acids Research·N Dinuka AbeydeeraXianbin Yang
Mar 1, 1997·Journal of Molecular Recognition : JMR·X ChengR L Juliano
Oct 6, 1998·Annual Review of Biochemistry·S Verma, F Eckstein
Jul 14, 2000·Nucleosides, Nucleotides & Nucleic Acids·G TosquellasJ L Imbach
Dec 3, 2016·Current Protocols in Nucleic Acid Chemistry·Xinhui LouXianbin Yang
Aug 3, 2017·International Journal of Molecular Sciences·Shuaijian NiGe Zhang
May 23, 2002·Antisense & Nucleic Acid Drug Development·Jean-Charles BolognaFrançois Morvan
May 15, 1999·Nucleic Acids Research·P P LaktionovB Lebleu
Jan 1, 1995·Antisense Research and Development·G TarrasónJ Piulats
Sep 2, 2016·Current Protocols in Nucleic Acid Chemistry·Xianbin Yang
Jul 13, 2001·Pharmacology & Therapeutics·C J Wraight, P J White
Oct 31, 1998·Brain Research. Molecular Brain Research·S Peng HoT Lesher
Oct 18, 2000·Advanced Drug Delivery Reviews·S Wu-Pong