Combined Fmoc-Alloc strategy for a general SPPS of phosphoserine peptides; preparation of phosphorylation-dependent tau antisera

Shapiro, Gideon; Büchler, Dieter; Dalvit, Claudio; Frey, Peter; Fernández, María del Carmen; Gómez‐Lor, Berta; Pombo‐Villar, Esteban; Stauss, U.; Swoboda, Robert; Waridel, Caroline

doi:10.1016/s0968-0896(96)00211-8

Cited by 14 publications

(11 citation statements)

References 35 publications

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“…While the cyclopentyl group proved to be an excellent O-phosphono-protecting group for the Boc method, Fmoc-Ser[PO(OBzl)(OH)]-OH was useful for the Fmoc strategy. and Fmoc peptide synthesis strategy [75]. With this method, the standard Fmoc-SPPS strategy should be performed up to the phosposerine residue, at which point Alloc-Ser[PO (OCH 2 CH=CH 2 ) 2 ]-OH is introduced " (Fig.…”

Section: N-boc-o-diallylphosphoryl Serine and N-boc-o-diallyl-mentioning

confidence: 99%

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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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Section: N-boc-o-diallylphosphoryl Serine and N-boc-o-diallyl-mentioning

confidence: 99%

“…Extension of the peptide chain was carried out via individual amino acid couplings. The method was successfully applied for the preparation of a tau phosphopeptide (H-Lys-Ile-Gly-Ser(P)-ThrGlu-Asn-Leu-Lys-His-OH) [76].…”

Section: N-boc-o-diallylphosphoryl Serine and N-boc-o-diallyl-mentioning

confidence: 99%

Phosphopeptides - Chemical Synthesis, Analysis, Outlook and Limitations.

Tóth¹,

Kele²,

Váradi³

2007

COC

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“…In a solid-phase synthesis of the Tau protein fragment 136, the amino acid unit 135 was linked to a hexapeptide assembled on Wang resin with the base-labile N-terminal Fmoc group and acid-labile side-chain protecting groups. [205] By Pd 0 -mediated release of the allyl protecting groups in the presence of Me 3 SiN 3 /Bu 4 NF, the N terminus and the phosphate group were simultaneously deblocked without b-elimination. Extension of the peptide chain and subsequent release of the phosphopeptide from the resin, with simultaneous cleavage of the side-chain protecting groups, gave the desired peptide 136.…”

Section: Phosphopeptides and Glycophosphopeptidesmentioning

confidence: 99%

Organic Synthesis and Biological Signal Transduction

Hinterding¹,

Alonso-Díaz²,

Waldmann³

1998

Angewandte Chemie International Edition

136

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The understanding of cellular communication pathways in molecular detail is an important goal of bioorganic research. The synthesis of analogues of active substances (e.g. 1) to study the regulation of muscle contraction or the specific lipid modification of representative peptides (→2) to investigate their subcellular, targeted transfer to intracellular membranes are examples of the capability of organic synthesis is in the research of biological signal transduction mechanisms.

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“…3,9 In this context, the 9-fluorenylmethoxycarbonyl/tert-butyl (Fmoc/t-Bu) solid-phase peptide synthesis (SPPS) strategy has proven to be especially valuable. 3,5,6,9 However, there are challenges associated with phosphopeptide synthesis using Fmoc/t-Bu SPPS and improvements in speed and efficiency as well as the complexity and diversity of the resulting phosphopeptides are desirable. 3 Towards this end we report here the development of a novel Fmoc/t-Bu SPPS strategy suitable for the efficient generation of structurally diverse phosphoserine-based peptides.…”

mentioning

confidence: 99%

“…8 In most cells, a large proportion of total protein phosphorylation occurs on serine residues; as such, there has been significant effort directed towards the development of methods for the incorporation of phosphoserine-based residues into artificial peptide chains. 3,9 In this context, the 9-fluorenylmethoxycarbonyl/tert-butyl (Fmoc/t-Bu) solid-phase peptide synthesis (SPPS) strategy has proven to be especially valuable. 3,5,6,9 However, there are challenges associated with phosphopeptide synthesis using Fmoc/t-Bu SPPS and improvements in speed and efficiency as well as the complexity and diversity of the resulting phosphopeptides are desirable.…”

mentioning

confidence: 99%

Novel Phosphate Derivatives as Scaffolds for the Preparation of Synthetic Phosphoserine-Based Peptides Using the Fmoc/t-Bu Solid-Phase Strategy

Cilibrizzi¹,

Isidro‐Llobet²,

Mateu³

et al. 2011

Synlett

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Synthetic peptides incorporating analogues of phosphoserine are valuable tools for the study of protein kinases and phosphatases. In addition, derivatives of naturally occurring peptides incorporating phosphate groups may have interesting biological properties. Herein we describe a new Fmoc/t-Bu solid-phase peptide synthesis (SPPS) strategy for the convenient generation of phosphoserine-based peptides. A proof-of-concept synthesis that demonstrates the feasibility of this approach is presented.Protein phosphorylation and dephosphorylation reactions are reversible processes, catalysed by kinases and phosphatases respectively, which play a key role in the regulation of cell function, growth and homeostasis. 1-3 Many diseases, including cancer, result from perturbations in the activity, or level of expression, of these enzymes. 4 Consequently the study of how nature orchestrates these opposing processes is a subject of considerable interest. 1,3 Synthetic peptides incorporating phosphorylated amino acid residues and their analogues (so-called phosphopeptides) have proven to be valuable tools for such investigations. 1,5-7 Furthermore derivatives of naturally occurring peptides incorporating phosphorylated amino acid residues (including serines) may have other interesting, potentially useful, biological properties. 8In most cells, a large proportion of total protein phosphorylation occurs on serine residues; as such, there has been significant effort directed towards the development of methods for the incorporation of phosphoserine-based residues into artificial peptide chains. 3,9 In this context, the 9-fluorenylmethoxycarbonyl/tert-butyl (Fmoc/t-Bu) solid-phase peptide synthesis (SPPS) strategy has proven to be especially valuable. 3,5,6,9 However, there are challenges associated with phosphopeptide synthesis using Fmoc/t-Bu SPPS and improvements in speed and efficiency as well as the complexity and diversity of the resulting phosphopeptides are desirable. 3 Towards this end we report here the development of a novel Fmoc/t-Bu SPPS strategy suitable for the efficient generation of structurally diverse phosphoserine-based peptides. As a proof-ofconcept this approach was applied to the synthesis of 1, a phosphorylated derivative of auto-inducing peptide III (AIP-III), a naturally occurring molecule involved in the regulation of quorum sensing in the Gram positive bacterium Staphylococcus aureus (Figure 1). 10 Non-natural analogues of AIPs hold significant value as chemical probes for studies on this intercellular signaling process and the delineation of structure-activity relationships may allow the rational development of antagonists which could potentially be used in a therapeutic context. 10a Figure 1 Structure of AIP-III and the phosphoserine-based derivative 1

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Combined Fmoc-Alloc strategy for a general SPPS of phosphoserine peptides; preparation of phosphorylation-dependent tau antisera

Cited by 14 publications

References 35 publications

Phosphopeptides - Chemical Synthesis, Analysis, Outlook and Limitations.

Phosphopeptides - Chemical Synthesis, Analysis, Outlook and Limitations.

Organic Synthesis and Biological Signal Transduction

Novel Phosphate Derivatives as Scaffolds for the Preparation of Synthetic Phosphoserine-Based Peptides Using the Fmoc/t-Bu Solid-Phase Strategy

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