Tagged small molecule library approach for facilitated chemical genetics

Acc Chem Res. 2007 Oct;40(10):1025-33. doi: 10.1021/ar700030k. Epub 2007 Jun 5.

Abstract

Chemical genetics is a powerful method which utilizes small molecule regulators to reveal the molecular basis of diverse biological processes. However, the current chemical genetic approach sometimes meets a serious bottleneck during the process of target identification. One faces difficulty in conjugating the active compound to an affinity matrix without losing or reducing its activity that leads to laborious structure-activity relationship (SAR) studies. To facilitate this process, we have developed a tagged triazine library containing a built-in linker that provides a straightforward transition from phenotypic screening to target identification. A strategy for constructing a tagged library and applications with a streamlined target identification and subsequent mechanistic study are discussed in this Account.

MeSH terms

  • Animals
  • Brain / embryology
  • Eye / embryology
  • Genetics*
  • Melanocytes / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Pigmentation
  • Zebrafish