Identification of DNA--cisplatin adducts in a blind trial of in situ scanning tunneling microscopy.
Scanning tunneling microscopy (STM) reveals nanometer scale details of hydrated DNA but the interpretation of the images is controversial because of substrate artifacts and the lack of a theory for image contrast. We demonstrate that we have overcome these problems by identifying five DNA samples by their STM images alone in a blinded trial. The samples were single-stranded and double-stranded DNA with and without covalent modification by the anti-tumor drug cisplatin. The cisplatin adducts were distinguished by substantial kinking at the drug binding site. The oligomers were 20 bases in length, which was too short to permit the kinking angle to be determined with precision. However, models with a 45 degree kink gave a better fit to the images of the duplex adducts than models with a 90 degrees kink. A variety of structures was observed for the single-stranded adducts.
Jeffrey
A M
AM
Department of Physics and Astronomy, Arizona State University, Tempe 85287.
Jing
T W
TW
DeRose
J A
JA
Vaught
A
A
Rekesh
D
D
Lu
F X
FX
Lindsay
S M
SM
D001483:Base Sequence; D002945:Cisplatin / Q000032:analysis*; D004247:DNA / Q000032:analysis*; D018736:DNA Adducts; D007091:Image Processing, Computer-Assisted; D008853:Microscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data
D018736:DNA Adducts; C057270:cisplatin-DNA adduct; D004247:DNA; D002945:Cisplatin