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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:25

Article

Hecht, Sidney M.¹ 

[1] Arizona State Univ, Ctr BioEnerget, Biodesign Inst, Tempe, AZ 85287 USA

关键词: Oxazole;    Thiazole;    Dipeptidomimetics;    Green fluorescent protein;    Modified ribosome;   

DOI  :  10.1016/j.bmcl.2015.08.073

来源: Elsevier

【 摘 要 】

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 alpha-amido-beta-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. (C) 2015 Elsevier Ltd. All rights reserved.

【 授权许可】

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