Inhibition of high affinity basic fibroblast growth factor binding by oligonucleotides.
Oligonucleotides can be used to inhibit the binding of basic fibroblast growth factor to cells. Though standard phosphodiester oligonucleotides show a slight inhibition of binding, the oligonucleotides with phosphorothioate internucleoside linkages have inhibition levels equivalent to that of the polyanion heparin. Variations in sequence of the oligonucleotides does lead to differences in the inhibitory action of the oligonucleotides. This inhibition of basic fibroblast growth factor by phosphorothioate oligonucleotides may account for much of the published data on inhibition of various genes by proposed antisense oligonucleotides and needs to be taken into account when considering the mechanism of action of oligonucleotides in biological systems.
Fennewald
S M
SM
Triplex Pharmaceutical Corporation, The Woodlands, Texas 77380, USA.
Rando
R F
RF
D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D002522:Chlorocebus aethiops; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology; D007700:Kinetics; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000494:pharmacology*; D017468:Receptors, Fibroblast Growth Factor / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013873:Thionucleotides; D014709:Vero Cells
D009838:Oligodeoxyribonucleotides; D017468:Receptors, Fibroblast Growth Factor; D013873:Thionucleotides; D016222:Fibroblast Growth Factor 2; D006493:Heparin