A phosphoarginine containing peptide as an artificial SH2 ligand

Hofmann, Frank T.; Lindemann, Claudia; Salia, Helen; Adamitzki, Philipp; Karanicolas, John; Seebeck, Florian P.

doi:10.1039/c1cc13341a

Cited by 23 publications

(24 citation statements)

References 30 publications

(32 reference statements)

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“…Important steps have been recently made towards the development of synthetic tools to allow the site-specific phosphorylation of native pLys and pArg peptides and mimetics of pHis in proteins 8 9 10 11 12 13 . These chemical tools have permitted the development of mass spectrometry (MS)-based methods or the generation of antibodies, leading to a better understanding of the biological role of these modifications 14 15 16 .…”

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confidence: 99%

Chemoselective synthesis and analysis of naturally occurring phosphorylated cysteine peptides

et al. 2016

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In contrast to protein O-phosphorylation, studying the function of the less frequent N- and S-phosphorylation events have lagged behind because they have chemical features that prevent their manipulation through standard synthetic and analytical methods. Here we report on the development of a chemoselective synthetic method to phosphorylate Cys side-chains in unprotected peptides. This approach makes use of a reaction between nucleophilic phosphites and electrophilic disulfides accessible by standard methods. We achieve the stereochemically defined phosphorylation of a Cys residue and verify the modification using electron-transfer higher-energy dissociation (EThcD) mass spectrometry. To demonstrate the use of the approach in resolving biological questions, we identify an endogenous Cys phosphorylation site in IICBGlc, which is known to be involved in the carbohydrate uptake from the bacterial phosphotransferase system (PTS). This new chemical and analytical approach finally allows further investigating the functions and significance of Cys phosphorylation in a wide range of crucial cellular processes.

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confidence: 99%

Chemoselective synthesis and analysis of naturally occurring phosphorylated cysteine peptides

et al. 2016

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“…[3c, 5] Despite the challenging nature of the N—P bond, chemical biologists have recently begun to focus on the development of suitable tools for analyzing protein N-phosphorylation. [3d, 6] For example, Muir and colleagues recently reported the development of the first pan-phospho-histidine (pHis) specific antibody using a stable triazole-based pHis analog as the hapten. [6c] …”

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“…[3d, 6] For example, Muir and colleagues recently reported the development of the first pan-phospho-histidine (pHis) specific antibody using a stable triazole-based pHis analog as the hapten. [6c] …”

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Synthesis and Use of a Phosphonate Amidine to Generate an Anti‐Phosphoarginine‐Specific Antibody

2015

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Protein arginine phosphorylation is a post-translational modification (PTM) that is important for bacterial growth and virulence. Despite its biological relevance, the intrinsic acid lability of phosphoarginine (pArg) have impaired studies of this novel PTM. Herein, we report for the first time the development of phosphonate-amidines and sulfonate-amidines as isosteres of pArg and then use these mimics as haptens to develop the first high affinity sequence independent anti-pArg specific antibody. Employing this anti-pArg antibody, we further showed that arginine phosphorylation is induced in Bacillus subtilis during oxidative stress. Overall, we expect this antibody to see widespread use in analyzing the biological significance of arginine phosphorylation. Additionally, the chemistry reported here will facilitate the generation of pArg mimetics as highly potent inhibitors of the enzymes that catalyze arginine phosphorylation/dephosphorylation.

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“…[98] These methods, however,a re inherently limited by their lack of sequence specificity.I nt his regard, recently reported solidphase peptide synthetic methods to prepare pLys-or pArgcontaining peptides with defined site specificity should be invaluable for further studies on these PTMs and hydrolase enzymes. [113][114][115] For example, the pLys peptides synthesized by using this method were pivotal in the investigation of gasphase phosphoryl transfer during electron-transfer dissociation (ETD) tandemMS. [116] It has also been ac hallenge to accurately measuret he hydrolase enzymea ctivities.…”

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confidence: 99%

Recent Updates on Protein N‐Phosphoramidate Hydrolases

2018

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In contrast to well‐recognized protein phosphorylation on the side‐chain oxygen of Ser, Thr, or Tyr residues, analogous phosphoramidation of the nitrogen of His, Lys, and Arg side chains remains much less investigated, mainly due to the instability of post‐translational modifications and technical difficulties involved in their analysis. For example, reports on the enzyme activities responsible for the formation and hydrolysis of these phosphoramidates date back to as early as the 1950s, but some of these enzymes have only recently been identified and functionally characterized; this has been aided by the development of novel research tools. In this review, we summarize current knowledge of the enzymes that hydrolyze protein N‐phosphoramidates, in terms of their structure, activities, and biological functions, as well as the chemical tools used to investigate them.

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A phosphoarginine containing peptide as an artificial SH2 ligand

Cited by 23 publications

References 30 publications

Chemoselective synthesis and analysis of naturally occurring phosphorylated cysteine peptides

Chemoselective synthesis and analysis of naturally occurring phosphorylated cysteine peptides

Synthesis and Use of a Phosphonate Amidine to Generate an Anti‐Phosphoarginine‐Specific Antibody

Recent Updates on Protein N‐Phosphoramidate Hydrolases

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