Solid‐phase synthesis of phosphopeptides

Ötvös, László; Elekes, I.; Lee, Virginta M‐Y.

doi:10.1111/j.1399-3011.1989.tb01501.x

Cited by 77 publications

(7 citation statements)

References 17 publications

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“…Fmoc deprotection steps were performed in two steps: 30 and 180 seconds, both at 45 W, 75 °C (Table and Scheme ). However, to minimize the risk of β ‐elimination of phosphate by piperidine, all Fmoc deprotection steps subsequent to phosphor‐amino acid coupling were performed without microwave irradiation for a longer duration: 300 and 900 seconds, both at 0 W, room temperature (Table and Scheme ) . A summary of peptide characterization is shown (Table ) as well as the HPLC and MS of the cyclic phosphopeptide final product (Figure ) (full characterization can be found in Figure S1).…”

Section: Methodsmentioning

confidence: 99%

“…Phosphopeptide synthesis can be achieved by two different approaches: in solution or on solid support. Solution‐based approaches have become less common, because they are laborious for larger phosphopeptides, which may suffer from solubility problems . Phosphopeptides can be synthesized using t‐butoxycarbonyl (Boc) or the 9‐fluorenylmethyloxycarbonyl group (Fmoc) orthogonal protection protocols using solid‐phase peptide synthesis (SPPS) .…”

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confidence: 99%

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Microwave‐assisted Synthesis of Cyclic Phosphopeptide on Solid Support

Qvit

2014

Chem Biol Drug Des

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Phosphopeptides are important tools for studying intracellular signal transduction events in vitro and in vivo and are also potential drugs due to their direct competition with phosphoprotein recognition elements. Cyclization has been demonstrated to improve peptide selectivity, metabolic stability, and bioavailability. However, cyclic phosphopeptide synthesis may not be straightforward due to the sterically hindered phosphorylated side-chain amino acid derivatives. One option to overcome this hurdle is to use microwave-assisted synthesis, which has been shown to increase efficiency and reduce synthesis time. Herein, a detailed protocol is provided for synthesizing cyclic phosphopeptides using automated microwave. The overall synthesis duration was reduced and yields increased compared with a manual conventional method. This method provides a general, fast and facile way to synthesize cyclic peptides, demonstrating the synthesis of cyclic phosphorylated peptides which are known to be among the most challenging to produce.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Microwave‐assisted Synthesis of Cyclic Phosphopeptide on Solid Support

Qvit

2014

Chem Biol Drug Des

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“…Solid-phase syntheses of phosphoserine-containing peptides have been reported by Otvos et al [86]. Serine residues left unprotected during the synthesis were phosphorylated with dibenzylphosphochloridate on the resin after the assembly of the peptide chain.…”

Section: 'Global' Approachmentioning

confidence: 98%

Phosphopeptides - Chemical Synthesis, Analysis, Outlook and Limitations.

Tóth¹,

Kele²,

Váradi³

2007

COC

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Protein phosphorylation is one of the most important post-translational events in cell regulation and signal transduction. Since the isolation of phosphorylated peptides from biological sources is usually not feasible, there is a need for efficient chemical phosphorylation methods to allow the study of the role of phosphorylation/dephosphorylation in biological processes. The recent developments in phosphopeptide chemistry (special protecting groups for the phosphate moiety and new amidite reagents) have provided peptide chemists with a wide variety of different strategies applicable for work with the sensitive phosphoserine, phosphothreonine and phosphotyrosine-containing peptides. This has made possible the efficient chemical preparation of longer, multiply phosphorylated, possibly cell-permeable or fluorescent residue-bearing peptides.

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“…11 Chemical peptide synthesis allows site-specific phosphorylation and provides an excellent method to obtain homogeneous phosphopeptides ( Fig.1B). 12,13 However, this is a very difficult approach and only a few successful examples were reported. [14][15][16][17] To carry out studies of the biological significance and roles of phosphorylation patterns feasible, there is a major unfulfilled need for a general synthetic method to access a library of multi-phosphorylated peptides at a low cost, high purity and sufficient yield.…”

Section: Introductionmentioning

confidence: 99%

A combinatorial approach for the synthesis of multi-phosphorylated peptides: new tool for studying phosphorylation patterns in proteins

Samarasimhareddy

Mayer

Metanis

et al. 2017

Preprint

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Phosphorylation of proteins at multiple sites creates different phosphorylation patterns that are essential for their biological activity. For example, such patterns contribute to the redirection of signalling to alternative pathways. Multi-phosphorylated peptides are excellent tools to systematically study the impact of unique phosphorylation patterns on signalling, but their synthesis is extremely difficult. Here we present an efficient and general method for the synthesis of multi-phosphorylated peptides, using a combination of different tailor-made coupling conditions. The method was demonstrated for the synthesis of a library of Rhodopsin C terminal peptides with distinct phosphorylation patterns containing up to seven phosphorylated Ser (pSer) and Thr (pThr) residues in close proximity to one another. Our method can be used to synthesize peptides incorporating multiple phosphorylated amino acids at high efficiency. It does not require any special expertise and can be performed in any standard peptide laboratory. This approach opens the way for quantitative mechanistic studies of phosphorylation patterns and their biological roles.

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Solid‐phase synthesis of phosphopeptides

Cited by 77 publications

References 17 publications

Microwave‐assisted Synthesis of Cyclic Phosphopeptide on Solid Support

Microwave‐assisted Synthesis of Cyclic Phosphopeptide on Solid Support

Phosphopeptides - Chemical Synthesis, Analysis, Outlook and Limitations.

A combinatorial approach for the synthesis of multi-phosphorylated peptides: new tool for studying phosphorylation patterns in proteins

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