An Efficient One‐Pot Four‐Segment Condensation Method for Protein Chemical Synthesis

Tang, Shan; Si, Yan-Yan; Wang, Zhipeng; Mei, Kunrong; Chen, Xin; Cheng, Jiongjia; Zheng, Ji‐Min; Liu, Lei

doi:10.1002/anie.201500051

Cited by 135 publications

(37 citation statements)

References 39 publications

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“…Finally,peptide 18 (1.2 equiv) was added to initiate the fourth NCL reaction. [13][14][15] At otal of seven steps were completed within 15 h; furthermore,t he concentration of the peptide elongated from the first peptide did not change greatly (initial, 2.1 mm ;f inal, 1.7 mm)b ecause only small amounts of additives were used for the entire synthetic procedure. The reaction product was purified by HPLC,a nd the desired peptide 19 was obtained in 59 %yield from 11,thus suggesting that each reaction step proceeded in 93 %y ield on average.…”

Section: Angewandte Chemiementioning

confidence: 99%

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

2018

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One-pot multiple peptide ligation is akey technology to improve the efficiency of chemical protein synthesis.O nepot repetitive peptide ligation requires ac ycle of three steps: peptide ligation, removal of ap rotecting group,a nd inactivation of the deprotection reagent. However,p revious strategies are not sufficient because of harsh deprotection conditions, slow deprotection rates,a nd difficulty in quenching the deprotection reagent. To address these issues,w ed eveloped ar apid, efficient deprotection and subsequent quenching strategy using an allyloxycarbonyl group to protect the Nterminal cysteine residue.4 -Mercaptophenylacetic acid (MPAA), at hiol additive for native chemical ligation, functioned not only as as cavenger for p-allyl palladium complexes,but also as aquencher of palladium(0) complexes. By utilizing the multifunctionality of MPAA, we carried out ao ne-pot five-segment ligation to affordh istone H2AX (142 amino acids), whichw as isolated in 59 %yield.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

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Section: Angewandte Chemiementioning

confidence: 99%

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

2018

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“…Unfortunately, we and others found that Thz was unstable under the hydrazide oxidation conditions, and Pentelute's group reported that an unproductive nitric oxide adduct might form . Although several N‐terminal Cys protecting groups have been reported to replace Thz, some of them are unstable to TCEP (a routine reductant in NCL), whereas others require long multistep syntheses . Luckily, we noticed that trifluoroacetyl (Tfa) protected primary or secondary amines could be mildly deprotected by treatment with aqueous base .…”

Section: Resultsmentioning

confidence: 99%

Synthesis of l‐ and d‐Ubiquitin by One‐Pot Ligation and Metal‐Free Desulfurization

Huang

Chen

Gao

et al. 2016

Chemistry A European J

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Native chemical ligation combined with desulfurization has become a powerful strategy for the chemical synthesis of proteins. Here we describe the use of a new thiol additive, methyl thioglycolate, to accomplish one-pot native chemical ligation and metal-free desulfurization for chemical protein synthesis. This one-pot strategy was used to prepare ubiquitin from two or three peptide segments. Circular dichroism spectroscopy and racemic protein X-ray crystallography confirmed the correct folding of ubiquitin. Our results demonstrate that proteins synthesized chemically by streamlined 9-fluorenylmethoxycarbonyl (Fmoc) solid-phase peptide synthesis coupled with a one-pot ligation-desulfurization strategy can supply useful molecules with sufficient purity for crystallographic studies.

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“…Two elegant studies exploited a specific cysteine protecting group strategy. 10,11 Another study relied on the differential reactivity of thiolester surrogates for setting up a kinetically controlled ligation scheme. 9 Fundamentally, the process described in Figure 4 differs from the previous studies in several aspects.…”

Section: Organic Lettersmentioning

confidence: 99%

Selectively Activatable Latent Thiol and Selenolesters Simplify the Access to Cyclic or Branched Peptide Scaffolds

2015

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The cyclic dichalcogenides based on the bis(2-chalcogenoethyl)amide structure are latent N,S (SEA, chalcogen = S) or N,Se (SeEA, chalcogen = Se) acyl shift systems. The large difference in the reducing potential between SEA and SeEA dichalcogenides allows their sequential and selective activation by reduction. Based on these concepts, one-pot three or four peptide segment assembly processes were designed, facilitating access to branched or cyclic peptide scaffolds.

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An Efficient One‐Pot Four‐Segment Condensation Method for Protein Chemical Synthesis

Cited by 135 publications

References 39 publications

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

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

Synthesis of l‐ and d‐Ubiquitin by One‐Pot Ligation and Metal‐Free Desulfurization

Selectively Activatable Latent Thiol and Selenolesters Simplify the Access to Cyclic or Branched Peptide Scaffolds

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