One‐Pot Four‐Segment Ligation Using Seleno‐ and Thioesters: Synthesis of Superoxide Dismutase

Takei, Toshiki; Andoh, Tomoshige; Takao, Toshifumi; Hojo, Hironobu

doi:10.1002/ange.201709418

Cited by 9 publications

(2 citation statements)

References 38 publications

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“…Takei et al have recently produced peptide selenophenyl esters by exchanging the N-ethyl cysteine N,S-acyl shift system by phenylselenol (Scheme 9). 290 In practice, selenophenol was generated in situ by reduction of diphenyldiselenide with TCEP, and the exchange was performed in aqueous acetonitrile containing acetic acid and 6 M urea.…”

Section: Chemical Reviewsmentioning

confidence: 99%

Native Chemical Ligation and Extended Methods: Mechanisms, Catalysis, Scope, and Limitations

et al. 2019

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The native chemical ligation reaction (NCL) involves reacting a C-terminal peptide thioester with an N-terminal cysteinyl peptide to produce a native peptide bond between the two fragments. This reaction has considerably extended the size of polypeptides and proteins that can be produced by total synthesis and has also numerous applications in bioconjugation, polymer synthesis, material science, and micro-and nanotechnology research. The aim of the present review is to provide a thorough mechanistic overview of NCL and extended methods. The most relevant properties of peptide thioesters, Cys peptides, and common solvents, reagents, additives, and catalysts used for these ligations are presented. Mechanisms, selectivity and reactivity are, whenever possible, discussed through the insights of computational and physical chemistry studies. The inherent limitations of NCL are discussed with insights from the mechanistic standpoint. This review also presents a palette of O,S-, N,S-, or N,Se-acyl shift systems as thioester or selenoester surrogates and discusses the special molecular features that govern reactivity in each case. Finally, the various thiol-based auxiliaries and thiol or selenol amino acid surrogates that have been developed so far are discussed with a special focus on the mechanism of long-range N,S-acyl migrations and selective dechalcogenation reactions.

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Section: Chemical Reviewsmentioning

confidence: 99%

Native Chemical Ligation and Extended Methods: Mechanisms, Catalysis, Scope, and Limitations

et al. 2019

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“…This ligation could also be achieved with selenoesters. Selenoester ligation could occur prior to thioester ligation, allowing the possibility of one‐pot kinetically controlled ligation for the assembly of superoxide dismutase, as Hojo and co‐workers have recently reported …”

Section: Other Ligation Techniquesmentioning

confidence: 99%

Chemical Protein Synthesis by Native Chemical Ligation and Variations Thereof

et al. 2019

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For a long time, the total synthesis of proteins was considered as a “mission impossible” because of the tedious and complex synthetic steps and demanding purification processes. However, with the development of modern synthetic methodologies, many protein syntheses have now been reported. More importantly, through chemical synthesis, desired modifications can be installed to target proteins precisely, which is a major advantage over traditional bio‐synthesis approaches. This review summarizes the techniques developed for protein assembly, including native chemical ligation, Se‐mediated ligation, and a range of other ligation methods. A few synthetic examples, whereby synthetic proteins with desired modifications have been utilized for related biological research, are also included. We believe that chemical synthesis can provide alternative pathways to solve problems that have hitherto proved insurmountable by traditional biological approaches.

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Triple Function of 4‐Mercaptophenylacetic Acid Promotes One‐Pot Multiple Peptide Ligation

2018

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One‐pot multiple peptide ligation is a key technology to improve the efficiency of chemical protein synthesis. One‐pot repetitive peptide ligation requires a cycle of three steps: peptide ligation, removal of a protecting group, and inactivation of the deprotection reagent. However, previous strategies are not sufficient because of harsh deprotection conditions, slow deprotection rates, and difficulty in quenching the deprotection reagent. To address these issues, we developed a rapid, efficient deprotection and subsequent quenching strategy using an allyloxycarbonyl group to protect the N‐terminal cysteine residue. 4‐Mercaptophenylacetic acid (MPAA), a thiol additive for native chemical ligation, functioned not only as a scavenger for π‐allyl palladium complexes, but also as a quencher of palladium(0) complexes. By utilizing the multifunctionality of MPAA, we carried out a one‐pot five‐segment ligation to afford histone H2AX (142 amino acids), which was isolated in 59 % yield.

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One‐Pot Four‐Segment Ligation Using Seleno‐ and Thioesters: Synthesis of Superoxide Dismutase

Cited by 9 publications

References 38 publications

Native Chemical Ligation and Extended Methods: Mechanisms, Catalysis, Scope, and Limitations

Native Chemical Ligation and Extended Methods: Mechanisms, Catalysis, Scope, and Limitations

Chemical Protein Synthesis by Native Chemical Ligation and Variations Thereof

Triple Function of 4‐Mercaptophenylacetic Acid Promotes One‐Pot Multiple Peptide Ligation

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