Elasticity of cisplatin-bound DNA reveals the degree of cisplatin binding.
Cisplatin was incidentally discovered to suppress cell division and became one of the most successful antitumor drugs. It is therapeutically active upon binding to DNA and locally kinking it. We demonstrate that after a bimodal modeling, the degree of platination of a single DNA molecule can be consistently and reliably estimated from elasticity measurements performed with magnetic tweezers. We predicted and measured for the first time two separate persistence lengths of kinked DNA at high and low tensions. We also directly observed that the degree of platination of DNA strongly depends on the concentration of sodium chloride as required for cisplatin's intracellular activity. Our study shows that micromanipulation techniques accurately reveal the degree of chemical modification of DNA which can be used for a new type of structure-sensitive biosensors.
Lee
Nam-Kyung
NK
Institute of Fundamental Physics, Department of Physics, Sejong University, Seoul 143-743, Korea.
Park
Jin-Sung
JS
Johner
Albert
A
Obukhov
Sergei
S
Hyon
Ju-Yong
JY
Lee
Kyoung J
KJ
Hong
Seok-Cheol
SC
D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism; D002945:Cisplatin / Q000737:chemistry* / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D018736:DNA Adducts / Q000737:chemistry* / Q000378:metabolism; D004548:Elasticity; D008956:Models, Chemical; D008958:Models, Molecular; D009690:Nucleic Acid Conformation
D000970:Antineoplastic Agents; D018736:DNA Adducts; C057270:cisplatin-DNA adduct; D004247:DNA; D002945:Cisplatin