The Experts below are selected from a list of 351 Experts worldwide ranked by ideXlab platform
Chuan-fa Liu - One of the best experts on this subject based on the ideXlab platform.
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A new method of N to C sequential ligation using Thioacid capture ligation and native chemical ligation.
Royal Society open science, 2018Co-Authors: Wen Hou, Lei Liu, Xiaohong Zhang, Chuan-fa LiuAbstract:Sequential peptide ligation strategy becomes more and more important in large protein or long peptides chemical synthesis due to the limited peptide/protein size obtained by solid phase synthesis of individual peptides or even one-step peptide ligation. Herein, we developed an alternative method which could perform the sequential peptide ligation of several segments from N to C direction based on the combined use of Thioacid capture ligation and native chemical ligation. The sweet protein monellin was produced through this strategy on a scale of multi-milligrams.
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synthesis of histone h3 proteins by a Thioacid capture ligation strategy
Chemical Communications, 2011Co-Authors: Xiaohong Zhang, Chuan-fa LiuAbstract:The first application of Thioacid capture ligation in protein synthesis is described. Two histone H3 proteins were synthesized in which a 30 min ligation reaction gave the protein products in good yields.
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protein c terminal modification through Thioacid azide amidation
Bioconjugate Chemistry, 2009Co-Authors: Xiaohong Zhang, Chuan-fa LiuAbstract:The preparation of protein bioconjugates has been largely dependent on the development of selective chemistries that are orthogonal to the diverse functionalities present in a protein. Here, we report a new method for C-terminus-directed modification of recombinant proteins. The method is based on the Thioacid/azide amidation reaction. Essentially, hydrothiolytic cleavage of the thioester intermediate in protein splicing yields a recombinant protein with a unique Thioacid group at the C-terminus, which is then chemoselectively amidated with an electron-poor organic azide carrying a biofunctional tag. The small ubiquitin protein was used as a model system to demonstrate the utility of this new bioconjugation method. C-terminal PEGylation or biotinylation of ubiquitin was readily achieved through amidation of ubiquitin Thioacid with a sulfonazide-functionalized PEG or biotin derivative. Our data validate that Thioacid/azide amidation is a mechanistically novel and practically useful method for site-selective protein modification.
Xiaohong Zhang - One of the best experts on this subject based on the ideXlab platform.
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A new method of N to C sequential ligation using Thioacid capture ligation and native chemical ligation.
Royal Society open science, 2018Co-Authors: Wen Hou, Lei Liu, Xiaohong Zhang, Chuan-fa LiuAbstract:Sequential peptide ligation strategy becomes more and more important in large protein or long peptides chemical synthesis due to the limited peptide/protein size obtained by solid phase synthesis of individual peptides or even one-step peptide ligation. Herein, we developed an alternative method which could perform the sequential peptide ligation of several segments from N to C direction based on the combined use of Thioacid capture ligation and native chemical ligation. The sweet protein monellin was produced through this strategy on a scale of multi-milligrams.
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synthesis of histone h3 proteins by a Thioacid capture ligation strategy
Chemical Communications, 2011Co-Authors: Xiaohong Zhang, Chuan-fa LiuAbstract:The first application of Thioacid capture ligation in protein synthesis is described. Two histone H3 proteins were synthesized in which a 30 min ligation reaction gave the protein products in good yields.
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protein c terminal modification through Thioacid azide amidation
Bioconjugate Chemistry, 2009Co-Authors: Xiaohong Zhang, Chuan-fa LiuAbstract:The preparation of protein bioconjugates has been largely dependent on the development of selective chemistries that are orthogonal to the diverse functionalities present in a protein. Here, we report a new method for C-terminus-directed modification of recombinant proteins. The method is based on the Thioacid/azide amidation reaction. Essentially, hydrothiolytic cleavage of the thioester intermediate in protein splicing yields a recombinant protein with a unique Thioacid group at the C-terminus, which is then chemoselectively amidated with an electron-poor organic azide carrying a biofunctional tag. The small ubiquitin protein was used as a model system to demonstrate the utility of this new bioconjugation method. C-terminal PEGylation or biotinylation of ubiquitin was readily achieved through amidation of ubiquitin Thioacid with a sulfonazide-functionalized PEG or biotin derivative. Our data validate that Thioacid/azide amidation is a mechanistically novel and practically useful method for site-selective protein modification.
Ailan Lee - One of the best experts on this subject based on the ideXlab platform.
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gold i catalyzed addition of thiols and Thioacids to 3 3 disubstituted cyclopropenes
ChemInform, 2012Co-Authors: Richard Mudd, Paul C Young, James A Jordanhore, Georgina M Rosair, Ailan LeeAbstract:Treatment of cyclopropenes of type (I) with thiols in the presence of AUC results in regio- and chemoselective formation of vinylic thioethers like (III).
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gold i catalyzed addition of thiols and Thioacids to 3 3 disubstituted cyclopropenes
Journal of Organic Chemistry, 2012Co-Authors: Richard Mudd, Paul C Young, James A Jordanhore, Georgina M Rosair, Ailan LeeAbstract:Gold(I)-catalyzed reactions of thiols, thiophenols, and Thioacids with 3,3-disubstituted cyclopropenes occur in a regioselective and chemoselective manner to produce either vinyl thioethers or primary allylic thioesters in good yields. A survey of commonly used gold(I) catalysts shows Echavarren’s cationic gold(I) catalyst to be most tolerant of deactivation by sulfur. A novel digold with bridging thiolate complex is characterized by X-ray crystallography, shedding light on a possible deactivation pathway.
Yasuhiro Kajihara - One of the best experts on this subject based on the ideXlab platform.
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glycoprotein semisynthesis by chemical insertion of glycosyl asparagine using a bifunctional Thioacid mediated strategy
Journal of the American Chemical Society, 2021Co-Authors: Kota Nomura, Yuta Maki, Ryo Okamoto, Ayano Satoh, Yasuhiro KajiharaAbstract:Glycosylation is a major modification of secreted and cell surface proteins, and the resultant glycans show considerable heterogeneity in their structures. To understand the biological processes arising from each glycoform, the preparation of homogeneous glycoproteins is essential for extensive biological experiments. To establish a more robust and rapid synthetic route for the synthesis of homogeneous glycoproteins, we studied several key reactions based on amino Thioacids. We found that diacyl disulfide coupling (DDC) formed with glycosyl asparagine Thioacid and peptide Thioacid yielded glycopeptides. This efficient coupling reaction enabled us to develop a new glycoprotein synthesis method, such as the bifunctional Thioacid-mediated strategy, which can couple two peptides with the N- and C-termini of glycosyl asparagine Thioacid. Previous glycoprotein synthesis methods required valuable glycosyl asparagine in the early stage and subsequent multiple glycoprotein synthesis routes, whereas the developed concept can generate glycoproteins within a few steps from peptide and glycosyl asparagine Thioacid. Herein, we report the characterization of the DDC of amino Thioacids and the efficient ability of glycosyl asparagine Thioacid to be used for robust glycoprotein semisynthesis.
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a chemoselective peptide bond formation by amino Thioacid coupling
Chemistry Letters, 2019Co-Authors: Ryo Okamoto, Kota Nomura, Yuta Maki, Yasuhiro KajiharaAbstract:Enzymes and ribosomes accurately form peptide bonds without protecting groups in vivo. Inspired by biological chemistries, we have been exploring a chemoselective reaction for peptide bond formatio...
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regioselective α peptide bond formation through the oxidation of amino Thioacids
Biochemistry, 2019Co-Authors: Ryo Okamoto, Takuya Haraguchi, Kota Nomura, Yuta Maki, Masayuki Izumi, Yasuhiro KajiharaAbstract:Biological systems, including ribosomes and enzymes, produce peptides with an extraordinary high speed and accuracy. On the other hand, a rational and regioselective α-peptide bond formation, without involving protecting groups, is difficult to achieve in chemical synthesis. In this study, α-amino Thioacids were utilized for the generation of polypeptides without using any protecting groups. We found that an α-amino Thioacid could oxidatively form a diaminoacyl-disulfide moiety and undergo a subsequent intramolecular S- to N-acyl transfer to form an α-peptide bond. Even the Thioacid form of lysine, which has a free e-amino group, generated a regioselective α-peptide bond. The oxidation of amino Thioacids generated the oligomers of amino acids. Interestingly, this oligomerization reaction proceeded even in the presence of iron ore, a prebiotic element, thus suggesting a plausible prebiotic peptide bond forming reaction.
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Regioselective α‑Peptide Bond Formation Through the Oxidation of Amino Thioacids
2019Co-Authors: Ryo Okamoto, Takuya Haraguchi, Kota Nomura, Yuta Maki, Masayuki Izumi, Yasuhiro KajiharaAbstract:Biological systems, including ribosomes and enzymes, produce peptides with an extraordinary high speed and accuracy. On the other hand, a rational and regioselective α-peptide bond formation, without involving protecting groups, is difficult to achieve in chemical synthesis. In this study, α-amino Thioacids were utilized for the generation of polypeptides without using any protecting groups. We found that an α-amino Thioacid could oxidatively form a diaminoacyl-disulfide moiety and undergo a subsequent intramolecular S- to N-acyl transfer to form an α-peptide bond. Even the Thioacid form of lysine, which has a free ε-amino group, generated a regioselective α-peptide bond. The oxidation of amino Thioacids generated the oligomers of amino acids. Interestingly, this oligomerization reaction proceeded even in the presence of iron ore, a prebiotic element, thus suggesting a plausible prebiotic peptide bond forming reaction
Valentin Wittmann - One of the best experts on this subject based on the ideXlab platform.
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application of the Thioacid azide ligation tal for the preparation of glycosylated and fluorescently labeled amino acids
Israel Journal of Chemistry, 2015Co-Authors: Katja Rohmer, Jamsad Mannuthodikayil, Valentin WittmannAbstract:The reaction of thiocarboxylic acids with azides (Thioacid-azide ligation, TAL) is a chemoselective transformation, leading to the formation of amide bonds. Especially in the case of electron-deficient sulfonyl azides, the reaction occurs in excellent yields, within minutes at room temperature, in a broad range of solvents. In this article, the application of TAL for the synthesis of glycosylated and dansylated amino acids is reported. 2-Azidosulfonylethyl glycosides were prepared from peracetylated monosaccharides and reacted with Thioacid-containing derivatives of aspartic acid and glutamic acid. Likewise, aromatic sulfonyl azides were employed. Ligation products were obtained in yields of up to 96 %. Different conditions for the generation of the Thioacids were compared. Whereas reaction of succinimidyl esters with sodium hydrogen sulfide led to concomitant formation of diacyl disulfides, trityl thioesters turned out to be suitable precursors for the in situ preparation of Thioacids by mild acidolysis.
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Preparation of Thioacid-Containing Amino Acids and Peptides and Their Application in Ligation Reactions
Peptides, 2010Co-Authors: Katja Rohmer, Jamsad Mannuthodikayil, Odin Keiper, Valentin WittmannAbstract:Introduction Ligation reactions have emerged as an important tool for the chemoselective conjugation of large and complex molecules. One recent example is the reaction of thiocarboxylic acids (Thioacids) with electron-deficient organic azides, such as sulfonyl azides [1]. This reaction proceeds at room temperature in different solvents and leads to N-acylsulfonamides in excellent yields. In the peptide field, this ligation reaction has been applied for the synthesis of neoglycopeptides [2], peptide mimetics [3], C-terminal labeling of peptide Thioacids [4], and labeling of sulfonyl azide-modified peptides [5]. Here we present the preparation of hitherto unknown amino acids and peptides with protected side chain Thioacids and their application in ligation reactions with sulfonyl azide-substituted carbohydrates.
