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Chemical Approaches to Studying Labile Amino Acid Phosphorylation

Abstract

Phosphorylation of serine, threonine, and tyrosine residues is the archetypal posttranslational modification of proteins. While phosphorylation of these residues has become standard textbook knowledge, phosphorylation of other amino acid side chains is underappreciated and minimally characterized by comparison. This disparity is rooted in the relative instability of these chemically distinct amino acid side chain moieties, namely phosphoramidates, acyl phosphates, thiophosphates, and phosphoanhydrides. In the case of the O-phosphorylated amino acids, synthetic constructs were critical to assessing their stability and developing tools for their study. As the chemical biology community has become more aware of these alternative phosphorylation sites, methodology has been developed for the synthesis of well-characterized standards and close mimics of these phosphorylated amino acids as well. In this article, we review the synthetic chemistry that is a prerequisite to progress in this field.

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Correspondence to Dorothea Fiedler.

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A. M. Marmelstein and J. Moreno contributed equally.

This article is part of the Topical Collection “Phosphate Labeling and Sensing in Chemical Biology”; edited by Henning Jessen.

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Marmelstein, A.M., Moreno, J. & Fiedler, D. Chemical Approaches to Studying Labile Amino Acid Phosphorylation. Top Curr Chem (Z) 375, 22 (2017). https://doi.org/10.1007/s41061-017-0111-1

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  • DOI: https://doi.org/10.1007/s41061-017-0111-1

Keywords

  • Posttranslational modification
  • Protein phosphorylation
  • Phosphohistidine
  • Phosphoarginine
  • Phospholysine
  • Pyrophosphorylation