Interferon-gamma-inhibitory oligodeoxynucleotides alter the conformation of interferon-gamma.

Abstract

The aptamer mechanism of action involves the direct interaction of oligonucleotide with protein and is responsible for the biological effects of many pharmacologically active oligodeoxynucleotides. In the work reported here, we have determined the effects of aptamers on the secondary, tertiary, and quaternary structures of the proteins with which they interact using interferon-gamma and the interferon-gamma-inhibitory aptamer oligonucleotide, 5'-GGG GTT GGT TGT GTT GGG TGT TGT GT, as a model system. CD, fluorescence spectroscopy studies, and antibody binding studies in this system demonstrate that the interferon-gamma-inhibitory 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, and the results suggest that aptamer oligodeoxynucleotides can significantly alter the structure of the proteins they interact with.