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

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19 Citations (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.

Original languageEnglish
Pages (from-to)297-301
Number of pages5
JournalBiochemical and Biophysical Research Communications
Issue number1
Publication statusPublished - Jan 7 2011



  • Binding affinity constant
  • Non-small cell lung cancer
  • Optical tweezers
  • PD153035
  • Tyrosine kinase inhibitor
  • Wormlike chain model

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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