Interferon-γ-Inhibitory Oligodeoxynucleotides Alter the Conformation of Interferon-γ
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-γ and the interferon-γ-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-γ-inhibitory aptamer oligonucleotide causes significant changes in secondary and tertiary structures of interferon-γ. 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.
Footnotes
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Send reprint requests to: Dr. Murali Ramanathan, Dept. of Pharmaceutics, 543 Cooke Hall, SUNY at Buffalo, Buffalo, NY 14260-1200. E-mail: murali{at}acsu.buffalo.edu
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This work was supported by Grant 1R29-GM54087–01 from the National Institute of General Medical Sciences. Funding from the National Multiple Sclerosis Society is also gratefully acknowledged. M.R. is a member of the University-to-University Cooperative Research Project between Kanazawa University, Japan, and the State University of New York at Buffalo.
- Abbreviations:
- IFN-γ
- interferon-γ
- ANS
- 1,8-aminonaphthalene sulfonate
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- Received November 25, 1997.
- Accepted February 5, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
