Abstract
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.
Highlights
Our own studies progressed from the initial use of oligonucleotides as anti-herpesvirus agents on Vero and MRC-5 cells [9]
Because basic fibroblast growth factor binding, like herpes simplex virus adsorption, involves interaction with cell surface heparan sulfate, we investigated whether oligonucleotides would inhibit the binding of bFGF to cells
BFGF binding to cells is assayed by the incubation of radiolabeled bFGF with cell monolayers with subsequent wash conditions able to distinguish the low affinity heparan sulfate binding from the high affinity protein receptor-specific binding [29]
Summary
Our own studies progressed from the initial use of oligonucleotides as anti-herpesvirus agents on Vero and MRC-5 cells [9]. Because basic fibroblast growth factor (bFGF) binding, like herpes simplex virus adsorption, involves interaction with cell surface heparan sulfate, we investigated whether oligonucleotides would inhibit the binding of bFGF to cells. In this model of bFGF receptor activity, exogenously added heparin competes with cell surface heparan sulfate and inhibits bFGF activity through the disruption of the dimerization of the receptor.
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