Inherently Emissive Puromycin Analogues for Live Cell Labelling

Angew Chem Int Ed Engl. 2023 Jun 5;62(23):e202216784. doi: 10.1002/anie.202216784. Epub 2023 Apr 27.

Abstract

Puromycin derivatives containing an emissive thieno[3,4-d]-pyrimidine core, modified with azetidine and 3,3-difluoroazetidine as Me2 N surrogates, exhibit translation inhibition and bactericidal activity similar to the natural antibiotic. The analogues are capable of cellular puromycylation of nascent peptides, generating emissive products without any follow-up chemistry. The 3,3-difluoroazetidine-containing analogue is shown to fluorescently label newly translated peptides and be visualized in both live and fixed HEK293T cells and rat hippocampal neurons.

Keywords: Antibiotics; Fluorescence; Heterocycles; Labelling; Modified Nucleosides.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • HEK293 Cells
  • Humans
  • Peptides*
  • Puromycin / pharmacology
  • Rats

Substances

  • Puromycin
  • Peptides