Nucleic Acids Research, 1995, Vol. 23, No. 21 4239-4245
© 1995
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Binding of phosphorothioate oligodeoxynucleotides to basic fibroblast growth factor, recombinant soluble CD4, laminin and fibronectin is P-chirality independent
Columbia University, College of Physicians and Surgeons 630 West 168 Street, New York, NY 10032, USA 1Center of Molecular and Macromolecular Studies, Polish Academy of Sciences ul. Sienkiewicza 112, 90-363 Lodz, Poland
*To whom correspondence should be addressed
Received September 11, 1995. Accepted October 4, 1995.
Antisense oligodeoxynucleotides can selectively inhibit the expression of individual genes and thus have potential applications in anticancer and antiviral therapy. A critical prerequisite to their use as therapeutic agents is the understanding of their non-specific interactions with biological structures, e.g. proteins. In this study we examined the interactions of P-chlral phosphorothioate oligodeoxynucleotides with several proteins. The Rp- and Sp- diastereomers, and racemlc machine-made mixtures, or M-oligodeoxynucleotides were used independently as competitors of the binding of a probe, phosphodiester oligodeoxynucleotide bearing a 5' alkylating moiety, to rsCD4, bFGF and laminin. These oligodeoxynucleotides were also used as competitors of the binding of a non-alkylating probe M-phosphorothioate oligodeoxynucleotide, 5'–32P-SdT18 to fibronectin. The average values of and quantitative estimates for the IC50 of competition and the constant of competition (KJ of Rp-, Sp- and M- stereoisomers of several homo- and heteropolymer oligodeoxynucleotides were determined and compared. Surprisingly, in the proteins we studied, the values of IC50 and Kc for the Rp-, Sp- and M-oligodeoxynucleotides were essentially identical. Thus, the ability of the phosphorothioate oligodeoxynucleotides we employed, to bind to the proteins studied in this work, is virtually independent of P-chirality. Our results also imply that the role of the purine and pyrimidine bases in oligodeoxynucleotide-protein interactions, as well as the nature of the contact points (sulfur versus oxygen) between the oligomer and the protein, may be relatively unimportant.
+Present address: Lily Research Laboratories, Eli Lilly and Co., Indianapolis, IN 46285, USA
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