Label-free detection of small-molecule-protein interactions by using nanowire nanosensors

Wayne U. Wang, Chuo Chen, Keng Hui Lin, Ying Fang, Charles M. Lieber

Research output: Contribution to journalArticle

462 Citations (Scopus)

Abstract

Development of miniaturized devices that enable rapid and direct analysis of the specific binding of small molecules to proteins could be of substantial importance to the discovery of and screening for new drug molecules. Here, we report highly sensitive and label-free direct electrical detection of small-molecule inhibitors of ATP binding to Abl by using silicon nanowire field-effect transistor devices. Abl, which is a protein tyrosine kinase whose constitutive activity is responsible for chronic myelogenous leukemia, was covalently linked to the surfaces of silicon nanowires within microfluidic channels to create active electrical devices. Concentration-dependent binding of ATP and concentration-dependent inhibition of ATP binding by the competitive small-molecule antagonist STI-571 (Gleevec) were assessed by monitoring the nanowire conductance. In addition, concentration-dependent inhibition of ATP binding was examined for four additional small molecules, including reported and previously unreported inhibitors. These studies demonstrate that the silicon nanowire devices can readily and rapidly distinguish the affinities of distinct small-molecule inhibitors and, thus, could serve as a technology platform for drug discovery.

Original languageEnglish (US)
Pages (from-to)3208-3212
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number9
DOIs
StatePublished - Mar 1 2005

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Nanowires
Silicon
Adenosine Triphosphate
Equipment and Supplies
Proteins
Preclinical Drug Evaluations
Competitive Binding
Microfluidics
Drug Discovery
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Protein-Tyrosine Kinases
Technology
Imatinib Mesylate

Keywords

  • Chronic myclogenous leukemia
  • Drug discovery
  • Gleevec
  • Inhibitors
  • Kinase

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Label-free detection of small-molecule-protein interactions by using nanowire nanosensors. / Wang, Wayne U.; Chen, Chuo; Lin, Keng Hui; Fang, Ying; Lieber, Charles M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 9, 01.03.2005, p. 3208-3212.

Research output: Contribution to journalArticle

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