Synthesis of fluorescent dipeptidomimetics and their ribosomal incorporation into green fluorescent protein

Sandipan Roy Chowdhury, Rumit Maini, Larisa Dedkova, Sidney Hecht

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The synthesis and incorporation into position 66 of green fluorescent protein (GFP) by in vitro protein translation of novel oxazole and thiazole based dipeptidomimetics are described. The compounds may be regarded as GFP chromophore analogues, and are strongly fluorescent. An α-amido-β-ketoester intermediate was obtained via bisacylation of a protected glycine. The intermediate underwent dehydrative cyclization to afford the 1,3-oxazole and was treated with Lawesson's reagent to furnish the 1,3-thiazole. When these fluorophores were introduced into position 66 of GFP in place of Tyr66, the resulting GFP analogues exhibited fluorescence emission several-fold greater than wild-type GFP; the emission was also shifted to shorter wavelength. It may be noted that compared to the typical fluorophores formed in the natural and modified fluorescent proteins, the oxazole and thiazole fluorophores are completely stable and do not require activation by posttranslational modification to exhibit fluorescence.

Original languageEnglish (US)
Pages (from-to)4715-4718
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume25
Issue number21
DOIs
StatePublished - May 8 2015

Fingerprint

Green Fluorescent Proteins
Oxazoles
Thiazoles
Fluorophores
2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide
Fluorescence
Cyclization
Protein Biosynthesis
Post Translational Protein Processing
Chromophores
Glycine
Proteins
Chemical activation
Wavelength

Keywords

  • Dipeptidomimetics
  • Green fluorescent protein
  • Modified ribosome
  • Oxazole
  • Thiazole

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Synthesis of fluorescent dipeptidomimetics and their ribosomal incorporation into green fluorescent protein. / Roy Chowdhury, Sandipan; Maini, Rumit; Dedkova, Larisa; Hecht, Sidney.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 25, No. 21, 08.05.2015, p. 4715-4718.

Research output: Contribution to journalArticle

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