N-Alkyl cysteine-assisted thioesterification of peptides

Hojo, Hironobu; Onuma, Yuko; Akimoto, Yuri; Nakahara, Yuko; Nakahara, Yoshiaki

doi:10.1016/j.tetlet.2006.11.034

Cited by 186 publications

(116 citation statements)

References 28 publications

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“…S or N ! S acyl shift from the corresponding esters [102][103][104][105] or amides [106][107][108][109][110][111][112][113][114][115][116][117][118]. Each method has its inherent strengths and weaknesses [119], and we discuss those of the newer methods here.…”

Section: New Methods For Activated Peptide Synthesismentioning

confidence: 99%

New Methods for Chemical Protein Synthesis

Guan

Chaffey

Zeng

2014

Topics in Current Chemistry

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Chemical protein synthesis is a useful tool to generate pure proteins which are otherwise difficult to obtain in sufficient amounts for structure and property analysis. Additionally, because of the precise and flexible nature of chemical synthesis, it allows for controllable variation of protein sequences, which is valuable for understanding the relationships between protein structure and function. Despite the usefulness of chemical protein synthesis, it has not been widely adopted as a tool for protein characterization, mainly because of the lack of general and efficient methods for the preparation and coupling of peptide fragments and for the folding of polypeptide chains. To address these issues, many new methods have recently been developed in the areas of solid-phase peptide synthesis, peptide fragment assembly, and protein folding. Here we review these recent technological advances and highlight the gaps needing to be addressed in future research.

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Section: New Methods For Activated Peptide Synthesismentioning

confidence: 99%

New Methods for Chemical Protein Synthesis

Guan

Chaffey

Zeng

2014

Topics in Current Chemistry

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“…Thus, methylation of the thiol group prior to TFA treatment was required for its complete removal. As N-S acyl shift from the secondary amino group under acidic condition is known (36)(37)(38)(39), care has to be taken for the final deprotection, when these auxiliary groups are used.…”

Section: Solution To the Restriction Of Ligation Site In Ncl Methodsmentioning

confidence: 99%

“…Recently, several groups including us have developed post SPPS thioesterification methods via N-to S-acyl shift reaction (36)(37)(38)(39). As the peptide chain is stably immobilized by the amide bond to the resin during SPPS and no activation such as alkylation is required for thioesteri-fication, these methods realize simple and high yield synthesis of peptide thioester.…”

Section: Scheme 3 Schemementioning

confidence: 99%

Progress in the Ligation Chemistry for Glycoprotein Synthesis

Hojo

Katayama

Nakahara

2010

TIGG

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“…Methyl esterification to produce 6 was non-problematic [14], however amino condensation either provided starting material 6 or dimethylated 8 depending if the amino-protected 6 or free amine 7 was utilized (Entries 1 and 2 respectively, Table 1). While the Schiff-base method has been used in the construction of MeCys(Trt), repeated attempts to repeat Hojo and Nakahara's conditions only provided 8 [15]. A complimentary approach utilized O'Donnell's ketimine 9, which was produced in good yield after trans-imination [16].…”

Section: Attempts At N-methylation Of Cysteine Using Established Methodsmentioning

confidence: 99%

A viable synthesis of N‐methyl cysteine

Ruggles¹,

Flemer²,

Hondal³

2008

Biopolymers

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While a number of methods exist for the production of N-methyl amino acid derivatives, the methods for the production of N-methyl cysteine (MeCys) derivatives are suboptimal as they either have low yields or lead to significant sulfhydryl deprotection during the synthetic protocol. This paper focuses on the generation of MeCys and its subsequent use in Fmoc solid-phase peptide synthesis for the generation of N-methyl cystine containing peptides. Various methods for amino methylation of cysteine, in the presence of acid labile or acid stable sulfhydryl protecting groups, are compared and contrasted. Production of MeCys is best attained through formation of an oxazolidinone precursor obtained via cyclization of Fmoc-Cys(StBu)-OH. Following oxazolidinone ring opening, iminium ion reduction generates Fmoc-MeCys(StBu)-OH with an overall yield of 91%. The key to this procedure is using an electronically neutral Cys-derivative, as other polar Cys-derivatives gave poor results using the oxazolidinone procedure. Subsequently, the Fmoc-MeCys(StBu)-OH building block was used to replace a Cys residue with a MeCys residue in two peptide fragments that correspond to the active sites of glutaredoxin and thioredoxin reductase. The examples used here highlight the use of a MeCys(StBu) derivative, which allows for facile on-resin conversion to a MeCys(5-Npys) residue that can be subsequently used for intramolecular disulfide bond formation with concomitant cleavage of the peptide from the solid support.

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N-Alkyl cysteine-assisted thioesterification of peptides

Cited by 186 publications

References 28 publications

New Methods for Chemical Protein Synthesis

New Methods for Chemical Protein Synthesis

Progress in the Ligation Chemistry for Glycoprotein Synthesis

A viable synthesis of N‐methyl cysteine

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