Optimised Synthesis of the Bacterial Magic Spot (p)ppGpp Chemosensor PyDPA

Chembiochem. 2019 Jul 1;20(13):1717-1721. doi: 10.1002/cbic.201900013. Epub 2019 May 24.

Abstract

Guanosine penta- or tetraphosphate (pppGpp or ppGpp, respectively) is a nucleotide signalling molecule with a marked effect on bacterial physiology during stress. Its accumulation slows down cell metabolism and replication, supposedly leading to the formation of the antibiotic-tolerant persister phenotype. A specifically tailored fluorescent chemosensor, PyDPA, allows the detection of (p)ppGpp in solution with high selectivity, relative to that of other nucleotides. Herein, an optimised synthetic approach is presented that improves the overall yield from 9 to 67 % over 7 steps. The simplicity and robustness of this approach will allow groups investigating the many facets of (p)ppGpp easy access to this probe.

Keywords: fluorescence; guanosine phosphates; nucleotides; sensors; synthesis design.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Coordination Complexes / chemical synthesis*
  • Fluorescence
  • Fluorescent Dyes / chemical synthesis*
  • Guanosine Pentaphosphate / analysis*
  • Guanosine Pentaphosphate / chemistry
  • Guanosine Tetraphosphate / analysis*
  • Guanosine Tetraphosphate / chemistry
  • Pyrenes / chemical synthesis*
  • Zinc / chemistry

Substances

  • Coordination Complexes
  • Fluorescent Dyes
  • Pyrenes
  • Guanosine Tetraphosphate
  • Guanosine Pentaphosphate
  • Zinc