Coding and Conformational Properties of Oligonucleotides Modified with the Carcinogen N-2-Acetylaminofluorene*
- INSTITUTE OF CANCER RESEARCH, COLLEGE OF PHYSICIANS AND SURGEONS, COLUMBIA UNIVERSITY, NEW YORK, NEW YORK
- DEPARTMENT OF MEDICINE, COLLEGE OF PHYSICIANS AND SURGEONS, COLUMBIA UNIVERSITY, NEW YORK, NEW YORK
- DEPARTMENT OF CHEMISTRY, COLUMBIA UNIVERSITY, NEW YORK, NEW YORK
- DEPARTMENT OF BIOLOGICAL SCIENCES, COLUMBIA UNIVERSITY, NEW YORK, NEW YORK
Abstract
The present studies were undertaken to determine the mechanism by which attachment of the carcinogen N-2-acetylaminofluorene to guanosine residues in nucleic acids distors their structure and function. Oligonucleotides were modified with N-acetoxy-2-acetylaminofluorene, repurified, and their base compositions analyzed. Evidence is presented that acetylaminofluorene residues bound to guanosines in GpUpU, ApApG, or poly (U,G) inactivates their function in codon recognition. Circular dichroism spectra suggest that this is caused by gross conformational changes in these compounds involving both a rotation about the glycosidic bond of guanosine residues bearing N-2-acetylaminofluorene, as well as stacking interactions between the drug and bases adjacent to the substituted guanosine.
Footnotes
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↵ † Requests for reprints may be addressed to Dr. D. Grunberger, Institute of Cancer Research, 99 Fort Washington Avenue, New York, N.Y. 10032.
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↵ ‡ Fellow of the Alfred P. Sloan Foundation.
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↵ § Career Scientist of the Health Research Council of the City of New York (I-190).
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↵ * This research was supported by grant CA-02332 and GM-14825 from the U.S. Public Health Service.
