The application of the chemical array for biological study.

Isao Miyazaki, Siro Simizu, Hiroyuki Osada

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The identification of specific interactions between small molecules and human proteins of interest is a fundamental step in chemical biology and drug development. The small molecules that bind to specific proteins can be used as tools to study the functions of proteins and biological processes in cells. We have developed an efficient method to obtain novel binding ligands of human proteins by a chemical array approach. Our method includes the use of cell lysates that express proteins of interest fused with red fluorescent protein (RFP) and high-throughput screening by merged display analysis, which removes false positive signals from array experiments. To demonstrate large-scale ligand screening for various human proteins of interest, the gene library GLORIA (Gene Library of Osada Laboratory at RIKEN for chemical array analysis) has been established. Using the systematic platform, we detected novel inhibitors of carbonic anhydrase II. We also have shown that this screening method is useful not merely for ligand screening of proteins of interest, but also for gaining insight into structure-affinity relationships (SARs) and for studies of "fragment-based approach."Traditional fragment-based ligand discoveries have been demonstrated by using several technologies, such as NMR spectroscopy and X-ray crystallography and mass spectrometry. We present initial studies of fragment-based approach to binding assay by using the chemical array format.

Original languageEnglish
Pages (from-to)95-107
Number of pages13
JournalMethods in molecular biology (Clifton, N.J.)
Volume669
Publication statusPublished - 2010
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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