Affinity-driven peptide selection of an NFAT inhibitor more selective than cyclosporin A Academic Article Article uri icon

Overview

MeSH Major

  • Fatty Acids
  • Neoplasms

abstract

  • The flow of information from calcium-mobilizing receptors to nuclear factor of activated T cells (NFAT)-dependent genes is critically dependent on interaction between the phosphatase calcineurin and the transcription factor NFAT. A high-affinity calcineurin-binding peptide was selected from combinatorial peptide libraries based on the calcineurin docking motif of NFAT. This peptide potently inhibited NFAT activation and NFAT-dependent expression of endogenous cytokine genes in T cells, without affecting the expression of other cytokines that require calcineurin but not NFAT. Substitution of the optimized peptide sequence into the natural calcineurin docking site increased the calcineurin responsiveness of NFAT. Compounds that interfere selectively with the calcineurin-NFAT interaction without affecting calcineurin phosphatase activity may be useful as therapeutic agents that are less toxic than current drugs.

publication date

  • October 5, 1999

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.1126/science.285.5436.2129

PubMed ID

  • 10497131

Additional Document Info

start page

  • 2129

end page

  • 33

volume

  • 285

number

  • 5436