Determining the binding mode and binding affinity constant of tyrosine kinase inhibitor PD153035 to DNA using optical tweezers

Chih Ming Cheng, Yuarn Jang Lee, Wei Ting Wang, Chien Ting Hsu, Jing Shin Tsai, Chien Ming Wu, Keng Liang Ou, Tzu Sen Yang

研究成果: 雜誌貢獻文章

19 引文 斯高帕斯(Scopus)


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 KA=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.

頁(從 - 到)297-301
期刊Biochemical and Biophysical Research Communications
出版狀態已發佈 - 一月 7 2011


ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology