Screening the sequence selectivity of DNA-Binding molecules using a gold nanoparticle based colorimetric approach

被引:62
作者
Hurst, Sarah J.
Han, Min Su
Lytton-Jean, Abigail K. R.
Mirkin, Chad A.
机构
[1] Northwestern Univ, Int Inst Nanotechnol, Dept Chem, Evanston, IL 60208 USA
[2] Chung Ang Univ, Dept Chem, Seoul 156756, South Korea
关键词
D O I
10.1021/ac071253e
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
We have developed a novel competition assay that uses a gold nanoparticle (Au NP)-based, high-throughput colorimetric approach to screen the sequence selectivity of DNA-binding molecules. This assay hinges on the observation that the melting behavior of DNA-functionalized Au NP aggregates is sensitive to the concentration of the DNA-binding molecule in solution. When short, oligomeric hairpin DNA sequences were added to a reaction solution consisting of DNA-functionalized Au NP aggregates and DNA-binding molecules, these molecules may either bind to the An NP aggregate interconnects or the hairpin stems based on their relative affinity for each. This relative affinity can be measured as a change in the melting temperature (T-m) of the DNA-modified Au NP aggregates in solution. As a proof of concept, we evaluated the selectivity of 4',6-diamidiitio-2-phenylindone (an AT-specific binder), ethidium bromide (a nonspecific binder), and chromomycin A (a GC-specific binder) for six sequences of hairpin DNA having different numbers of AT pairs in a five-base pair variable stem region. Our assay accurately and easily confirmed the known trends in selectivity for the DNA binders in question without the use of complicated instrumentation. This novel assay will be useful in assessing large libraries of potential drug candidates that work by binding DNA to form a drug/DNA complex.
引用
收藏
页码:7201 / 7205
页数:5
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