INTERFERON-GAMMA-INHIBITORY OLIGODEOXYNUCLEOTIDES ALTER THE CONFORMATION OF INTERFERON-GAMMA

The aptamer mechanism of action involves the direct interaction of oli gonucleotide with protein and is responsible for the biological effect s of many pharmacologically active oligodeoxynucleotides. In the work reported here, we have determined the effects of aptamers on the secon dary, tertiary, and quaternary structures of the proteins with which t hey interact using interferon-gamma and the interferon-gamma-inhibitor y aptamer oligonucleotide, 5'-GGG GTT GGT TGT GTT GGG TGT TGT GT, as a model system. CD, fluorescence spectroscopy studies. and antibody bin ding studies in this system demonstrate that the interferon-gamma-inhi bitory aptamer oligonucleotide causes significant changes in secondary and tertiary structures of interferon-gamma. These structural changes do not result in, or resemble, protein denaturation or aggregation, a nd the results suggest that aptamer oligodeoxynucleotides can signific antly alter the structure of the proteins they interact with.