Fluorescent caged phosphoserine peptides as probes to investigate phosphorylation-dependent protein associations

J Am Chem Soc. 2003 Aug 27;125(34):10150-1. doi: 10.1021/ja0351847.

Abstract

The development of chemical probes for the investigation of the complex phosphorylation signaling cascades that regulate biological events is crucial to understanding these processes. We describe herein a bifunctional probe that enables spatial and temporal release of a biologically active ligand while allowing simultaneous monitoring of its binding to the protein of interest. Substitution of Tyr(-2) for the enviromentally sensitive fluorescent amino acid DANA in the sequence RLYRpSLPA which is known to bind the 14-3-3 protein does not adversely affect binding affinity and allows monitoring of the binding process. The binding of the peptide to 14-3-3 places the fluorescent reporter unit into a hydrophobic pocket, which changes the fluorescent maximum emission intensity and wavelength. At the same time, the newly developed photolabile 1-(2-nitrophenyl)ethyl-caged phosphoserine allows control of the release of the biologically active ligand through unmasking of the key phosphoserine functionality upon UV irradiation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 14-3-3 Proteins
  • 2-Naphthylamine / analogs & derivatives*
  • 2-Naphthylamine / chemistry
  • Alanine / analogs & derivatives*
  • Alanine / chemistry
  • Fluorescent Dyes / chemistry
  • Naphthalenes / chemistry
  • Phosphopeptides / chemistry*
  • Phosphorylation
  • Phosphoserine / chemistry*
  • Spectrometry, Fluorescence / methods*
  • Tyrosine 3-Monooxygenase / analysis*
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • 14-3-3 Proteins
  • 6-(2-dimethylaminonaphthoyl) alanine
  • Fluorescent Dyes
  • Naphthalenes
  • Phosphopeptides
  • Phosphoserine
  • prodan
  • 2-Naphthylamine
  • Tyrosine 3-Monooxygenase
  • Alanine