Interactions of gold coordination complexes with DNA.
The interactions of certain gold(I) and gold(III) complexes with isolated plasmid pBR322 DNA were defined and compared to those of cis-diamminedichloroplatinum(II), CDDP, using an agarose gel electrophoresis assay. Trichloro(pyridine)gold(III) appeared to bind to DNA as evidenced by its ability to produce dose-dependent changes in the electrophoretic mobilities of closed circular, supercoiled, closed circular, relaxed, and open circular plasmid DNAs. These effects suggest that the gold containing complex induces conformational changes in the plasmid as a result of the compound binding to the DNA and the subsequent unwinding of the double helix and shorting of the DNA. Auranofin [(2,3,4,6-tetra-O-acetyl-1-thio-beta-D-glucopyranosato-S)-triethyl phosphine gold(I)] did not appear to interact with DNA under any conditions. However, its analog chloro(triethylphosphine) gold(I) interacted with DNA at pH 9.5 in borate buffer and produced electrophoretic mobility changes in pBR322 DNA which were different from those produced by the gold(III) complexes that were evaluated. Binding of chloro(triethylphosphine) gold(I) was inhibited by the co-addition of the thiosugar portion of auranofin suggesting preferential binding of the gold moiety to thiosugar, which results in the production of auranofin (or a sugar containing) gold complex and inhibition of gold binding to DNA. The interactions of a number of gold compounds with DNA were also evidenced by their abilities to inhibit the binding of ethidium bromide to DNA. The results from these studies indicate that: gold containing complexes can bind to, and produce conformational changes in, DNA; gold(I) and gold(III) complexes may interact with DNA via different chemical mechanisms to produce different conformational changes in DNA; and certain coordinating ligands in gold complexes (e.g. Cl, Br and SCN) can be exchanged for binding sites on DNA by gold.
C K
CK
Mirabelli
C M
CM
Sung
J P
JP
Zimmerman
D T
DT
Hill
S
S
Mong
S T
ST
Crooke
D000818:Animals; D002417:Cattle; D002945:Cisplatin / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D004587:Electrophoresis, Agar Gel; D004996:Ethidium; D005453:Fluorescence; D006046:Gold / Q000378:metabolism / Q000494:pharmacology*; D008024:Ligands; D009690:Nucleic Acid Conformation; D010957:Plasmids; D013329:Structure-Activity Relationship
D008024:Ligands; D006046:Gold; D004247:DNA; D004996:Ethidium; D002945:Cisplatin