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

doi:10.1016/j.bbrc.2010.11.110

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

Research output: Contribution to journal › Article › peer-review

23 Citations (Scopus)

Abstract

Accurately predicting binding affinity constant (K_A) 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 K_A for PD153035, where K_A 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 language	English
Pages (from-to)	297-301
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	404
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2010.11.110
Publication status	Published - Jan 7 2011

Keywords

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

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bbrc.2010.11.110

Cite this

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

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 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.",

keywords = "Binding affinity constant, Non-small cell lung cancer, Optical tweezers, PD153035, Tyrosine kinase inhibitor, Wormlike chain model",

author = "Cheng, {Chih Ming} and Lee, {Yuarn Jang} and Wang, {Wei Ting} and Hsu, {Chien Ting} and Tsai, {Jing Shin} and Wu, {Chien Ming} and Ou, {Keng Liang} and Yang, {Tzu Sen}",

note = "Funding Information: C.M. Cheng and W.T. Wang contributed equally to this work. We acknowledge funding from the Taipei Medical University (TMU96-AE1-B36), Cathay General Hospital/Taipei Medical University (97CGH-TMU-15), and Taipei Medical University/Taipei Medical University Hospital (98TMU-TMUH-03-3 and 99TMU-TMUH-03-4). ",

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doi = "10.1016/j.bbrc.2010.11.110",

language = "English",

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T1 - Determining the binding mode and binding affinity constant of tyrosine kinase inhibitor PD153035 to DNA using optical tweezers

AU - Cheng, Chih Ming

AU - Lee, Yuarn Jang

AU - Wang, Wei Ting

AU - Hsu, Chien Ting

AU - Tsai, Jing Shin

AU - Wu, Chien Ming

AU - Ou, Keng Liang

AU - Yang, Tzu Sen

N1 - Funding Information: C.M. Cheng and W.T. Wang contributed equally to this work. We acknowledge funding from the Taipei Medical University (TMU96-AE1-B36), Cathay General Hospital/Taipei Medical University (97CGH-TMU-15), and Taipei Medical University/Taipei Medical University Hospital (98TMU-TMUH-03-3 and 99TMU-TMUH-03-4).

PY - 2011/1/7

Y1 - 2011/1/7

N2 - 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.

AB - 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.

KW - Binding affinity constant

KW - Non-small cell lung cancer

KW - Optical tweezers

KW - PD153035

KW - Tyrosine kinase inhibitor

KW - Wormlike chain model

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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