Limits...
Revealing Three Stages of DNA-Cisplatin Reaction by a Solid-State Nanopore.

Zhou Z, Hu Y, Shan X, Li W, Bai X, Wang P, Lu X - Sci Rep (2015)

Bottom Line: The interaction processes are found to be well elucidated by the evolution of the capture rate of DNA-cisplatin complex, which is defined as the number of their translocation events through the nanopore in unit time.In the second stage, by forming di-adducts, the capture rate increases as DNA molecules are softened, appears as the reduced persistence length of the DNA-cisplatin adducts.In the third stage, the capture rate decreases again as a result of DNA aggregation.

View Article: PubMed Central - PubMed

Affiliation: Beijing National Laboratory for Condensed-Matter Physics and Institute of Physics, Chinese Academy of Sciences, Beijing 100190, People's Republic of China.

ABSTRACT
The dynamic structural behavior in DNA due to interaction with cisplatin is essential for the functionality of platinum-based anti-cancer drugs. Here we report a novel method to monitor the interaction progress in DNA-cisplatin reaction in real time with a solid-state nanopore. The interaction processes are found to be well elucidated by the evolution of the capture rate of DNA-cisplatin complex, which is defined as the number of their translocation events through the nanopore in unit time. In the first stage, the capture rate decreases rapidly due to DNA discharging as the positive-charged hydrated cisplatin molecules initially bond to the negative-charged DNA and form mono-adducts. In the second stage, by forming di-adducts, the capture rate increases as DNA molecules are softened, appears as the reduced persistence length of the DNA-cisplatin adducts. In the third stage, the capture rate decreases again as a result of DNA aggregation. Our study demonstrates a new single-molecule tool in exploring dynamic behaviors during drug-DNA reactions and may have future application in fast drug screening.

No MeSH data available.


Stage II.(a) Capture rate versus reaction time. The driving voltage is 200 mV and the nanopore diameter is 5.3 nm. The solid line is the fitting result. Inset: schematic of DNA-cisplatin di-adducts. (b) Plot of the measured reduced persistence length versus reaction time. The solid line is the fitting result with equation (5). (c) Plot of the rate constant k2 versus concentration ratio α.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4493569&req=5

f4: Stage II.(a) Capture rate versus reaction time. The driving voltage is 200 mV and the nanopore diameter is 5.3 nm. The solid line is the fitting result. Inset: schematic of DNA-cisplatin di-adducts. (b) Plot of the measured reduced persistence length versus reaction time. The solid line is the fitting result with equation (5). (c) Plot of the rate constant k2 versus concentration ratio α.

Mentions: The bonded cisplatin molecule may have its second arm bond to a neighboring guanine or adenine base, forming a di-adduct (see the schematic image in the inset of Fig. 4a)4. The di-adduct bends the DNA molecule and decreases its persistence length. The linear charge density keeps constant during this stage, and the capture rate J can be simply represented as a function of persistence length:where A2 is a constant in the stage. The capture rate increases due to the reduction of persistence length. Figure 4a shows typical evolution of capture rate J in this stage. The concentration ratio α equals 1 in this data set and results are similar for α of 0.5 and 2.


Revealing Three Stages of DNA-Cisplatin Reaction by a Solid-State Nanopore.

Zhou Z, Hu Y, Shan X, Li W, Bai X, Wang P, Lu X - Sci Rep (2015)

Stage II.(a) Capture rate versus reaction time. The driving voltage is 200 mV and the nanopore diameter is 5.3 nm. The solid line is the fitting result. Inset: schematic of DNA-cisplatin di-adducts. (b) Plot of the measured reduced persistence length versus reaction time. The solid line is the fitting result with equation (5). (c) Plot of the rate constant k2 versus concentration ratio α.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493569&req=5

f4: Stage II.(a) Capture rate versus reaction time. The driving voltage is 200 mV and the nanopore diameter is 5.3 nm. The solid line is the fitting result. Inset: schematic of DNA-cisplatin di-adducts. (b) Plot of the measured reduced persistence length versus reaction time. The solid line is the fitting result with equation (5). (c) Plot of the rate constant k2 versus concentration ratio α.
Mentions: The bonded cisplatin molecule may have its second arm bond to a neighboring guanine or adenine base, forming a di-adduct (see the schematic image in the inset of Fig. 4a)4. The di-adduct bends the DNA molecule and decreases its persistence length. The linear charge density keeps constant during this stage, and the capture rate J can be simply represented as a function of persistence length:where A2 is a constant in the stage. The capture rate increases due to the reduction of persistence length. Figure 4a shows typical evolution of capture rate J in this stage. The concentration ratio α equals 1 in this data set and results are similar for α of 0.5 and 2.

Bottom Line: The interaction processes are found to be well elucidated by the evolution of the capture rate of DNA-cisplatin complex, which is defined as the number of their translocation events through the nanopore in unit time.In the second stage, by forming di-adducts, the capture rate increases as DNA molecules are softened, appears as the reduced persistence length of the DNA-cisplatin adducts.In the third stage, the capture rate decreases again as a result of DNA aggregation.

View Article: PubMed Central - PubMed

Affiliation: Beijing National Laboratory for Condensed-Matter Physics and Institute of Physics, Chinese Academy of Sciences, Beijing 100190, People's Republic of China.

ABSTRACT
The dynamic structural behavior in DNA due to interaction with cisplatin is essential for the functionality of platinum-based anti-cancer drugs. Here we report a novel method to monitor the interaction progress in DNA-cisplatin reaction in real time with a solid-state nanopore. The interaction processes are found to be well elucidated by the evolution of the capture rate of DNA-cisplatin complex, which is defined as the number of their translocation events through the nanopore in unit time. In the first stage, the capture rate decreases rapidly due to DNA discharging as the positive-charged hydrated cisplatin molecules initially bond to the negative-charged DNA and form mono-adducts. In the second stage, by forming di-adducts, the capture rate increases as DNA molecules are softened, appears as the reduced persistence length of the DNA-cisplatin adducts. In the third stage, the capture rate decreases again as a result of DNA aggregation. Our study demonstrates a new single-molecule tool in exploring dynamic behaviors during drug-DNA reactions and may have future application in fast drug screening.

No MeSH data available.