6-Thioguanine alters the structure and stability of duplex DNA and inhibits quadruplex DNA formation

The ability to chemically synthesize biomolecules has opened up the opportunity to observe changes in structure and activity that occur upon single atom substitution. In favorable cases this can provide information about the roles of individual atoms. The substitution of 6-thioguanine (6SG) for guan...

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Bibliographic Details
Published in:Nucleic acids research 1999-07, Vol.27 (14), p.2860-2867
Main Authors: Marathias, Vasilios M., Sawicki, Michele J., Bolton, Philip H.
Format: Article
Language:English
Subjects:
Base Pairing
Base Sequence
DNA - chemistry
DNA - genetics
DNA - metabolism
G-Quadruplexes
Guanine - analogs & derivatives
Guanine - chemistry
Guanine - metabolism
Nuclear Magnetic Resonance, Biomolecular
Nucleic Acid Conformation
Protons
Temperature
Thermodynamics
Thioguanine - chemistry
Thioguanine - metabolism
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Summary:The ability to chemically synthesize biomolecules has opened up the opportunity to observe changes in structure and activity that occur upon single atom substitution. In favorable cases this can provide information about the roles of individual atoms. The substitution of 6-thioguanine (6SG) for guanine is a potentially very useful single atom substitution as 6SG has optical, photocrosslinking, metal ion binding and other properties of potential utility. In addition, 6-mercaptopurine is a clinically important pro-drug that is activated by conversion into 6SG by cells. The results presented here indicate that the presence of 6SG blocks the formation of quadruplex DNA. The presence of 6SG alters the structure and lowers the thermal stability of duplex DNA, but duplex DNA can be formed in the presence of 6SG. These results indicate that some of the cytotoxic activity of 6SG may be due to disruption of the quadruplex structures formed by telomere and other DNAs. This additional mode of action is consistent with the delayed onset of cytotoxicity.
ISSN:0305-1048
1362-4962
1362-4962
DOI:10.1093/nar/27.14.2860