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Designing transcription factor architectures for drug discovery

Academic Article
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Overview

authors

  • Blancafort, P.
  • Segal, D. J.
  • Barbas III, Carlos

publication date

  • December 2004

journal

  • Molecular Pharmacology  Journal

abstract

  • Recent advances in the design, selection, and engineering of DNA binding proteins have led to the emerging field of designer transcription factors (TFs). Modular DNA-binding protein domains can be assembled to recognize a given sequence of a DNA in a regulatory region of a targeted gene. TFs can be readily prepared by linking the DNA-binding protein to a variety of effector domains that mediate transcriptional activation or repression. Furthermore, the interaction between the TF and the genomic DNA can be regulated by several approaches, including chemical regulation by a variety of small molecules. Genome-wide single target specificity has been demonstrated using arrays of sequence-specific zinc finger (ZF) domains, polydactyl proteins. Any laboratory today can easily construct polydactyl ZF proteins by linkage of predefined ZF units that recognize specific triplets of DNA. The potential of this technology to alter the transcription of specific genes, to discover new genes, and to induce phenotypes in cells and organisms is now being applied in the areas of molecular therapeutics, pharmacology, biotechnology, and functional genomics.

subject areas

  • Amino Acid Sequence
  • Base Sequence
  • Binding Sites
  • DNA
  • DNA-Binding Proteins
  • Drug Design
  • Gene Expression Regulation
  • Models, Molecular
  • Protein Conformation
  • Transcription Factors
  • Zinc Fingers
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Identity

International Standard Serial Number (ISSN)

  • 0026-895X

Digital Object Identifier (DOI)

  • 10.1124/mol.104.002758.

PubMed ID

  • 15340042
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Additional Document Info

start page

  • 1361

end page

  • 1371

volume

  • 66

issue

  • 6

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