1. Determining the binding mode and binding affinity constant of tyrosine kinase inhibitor PD153035 to DNA using optical tweezers
- Author
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Cheng, Chih-Ming, Lee, Yuarn-Jang, Wang, Wei-Ting, Hsu, Chien-Ting, Tsai, Jing-Shin, Wu, Chien-Ming, Ou, Keng-Liang, and Yang, Tzu-Sen
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PROTEIN-tyrosine kinase inhibitors , *DNA , *OPTICAL tweezers , *DRUG-DNA interactions , *THERMODYNAMICS , *LUNG cancer , *EPIDERMAL growth factor - Abstract
Abstract: Accurately predicting binding affinity constant (KA ) is highly required to determine the binding energetics of the driving forces in drug–DNA interactions. Recently, PD153035, brominated anilinoquinazoline, has been reported to be not only a highly selective inhibitor of epidermal growth factor receptor but also a DNA intercalator. Here, we use a dual-trap optical tweezers to determining KA for PD153035, where KA is determined from the changes in B-form contour length (L) of PD153035–DNA complex. Here, L is fitted using a modified wormlike chain model. We found that a noticeable increment in L in 1mM sodium cacodylate was exhibited. Furthermore, our results showed that =1.18(±0.09)×104 (1/M) at 23±0.5°C and the minimum distance between adjacent bound PD153035≈11bp. We anticipate that by using this approach we can determine the complete thermodynamic profiles due to the presence of DNA intercalators. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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