scholarly journals Insights into the Mechanism and Catalysis of Peptide Thioester Synthesis by Alkylselenols Provide a New Tool for Chemical Protein Synthesis

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1386
Author(s):  
Florent Kerdraon ◽  
Gemma Bogard ◽  
Benoît Snella ◽  
Hervé Drobecq ◽  
Muriel Pichavant ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Total Synthesis ◽  
Adaptive Immunity ◽  
Biologically Active ◽  
Acidic Ph ◽  
Innate And Adaptive Immunity ◽  
Chemotactic Protein ◽  
Chemical Protein Synthesis ◽  
Peptide Thioester ◽  
Peptide Thioesters

While thiol-based catalysts are widely employed for chemical protein synthesis relying on peptide thioester chemistry, this is less true for selenol-based catalysts whose development is in its infancy. In this study, we compared different selenols derived from the selenocysteamine scaffold for their capacity to promote thiol–thioester exchanges in water at mildly acidic pH and the production of peptide thioesters from bis(2-sulfanylethyl)amido (SEA) peptides. The usefulness of a selected selenol compound is illustrated by the total synthesis of a biologically active human chemotactic protein, which plays an important role in innate and adaptive immunity.

scholarly journals Insights into the Mechanism and Catalysis of Peptide Thioester Synthesis by Alkylselenols Provide a New Tool for Chemical Protein Synthesis

2021 ◽  
Author(s):  
Florent kerdraon ◽  
Gemma Bogard ◽  
Benoît Snella ◽  
Hervé Drobecq ◽  
Muriel Pichavant ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Total Synthesis ◽  
Adaptive Immunity ◽  
Biologically Active ◽  
Acidic Ph ◽  
Innate And Adaptive Immunity ◽  
Chemotactic Protein ◽  
Chemical Protein Synthesis ◽  
Peptide Thioester ◽  
Peptide Thioesters

While thiol-based catalysts are widely employed for chemical protein synthesis relying on peptide thioester chemistry, this is less true for selenol-based catalysts whose development is in its infancy. In this study, we compared different selenols derived from the selenocysteamine scaffold for their capacity to promote thiol-thioester exchanges in water at mildly acidic pH and the production of peptide thioesters from bis(2-sulfanylethyl)amido (SEA) peptides. The usefulness of a selected selenol compound is illustrated by the total synthesis of a biologically active human chemotactic protein, which plays an important role in innate and adaptive immunity<br>

scholarly journals Insights into the Mechanism and Catalysis of Peptide Thioester Synthesis by Alkylselenols Provide a New Tool for Chemical Protein Synthesis

2021 ◽  
Author(s):  
Florent kerdraon ◽  
Gemma Bogard ◽  
Benoît Snella ◽  
Hervé Drobecq ◽  
Muriel Pichavant ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Total Synthesis ◽  
Adaptive Immunity ◽  
Biologically Active ◽  
Acidic Ph ◽  
Innate And Adaptive Immunity ◽  
Chemotactic Protein ◽  
Chemical Protein Synthesis ◽  
Peptide Thioester ◽  
Peptide Thioesters

While thiol-based catalysts are widely employed for chemical protein synthesis relying on peptide thioester chemistry, this is less true for selenol-based catalysts whose development is in its infancy. In this study, we compared different selenols derived from the selenocysteamine scaffold for their capacity to promote thiol-thioester exchanges in water at mildly acidic pH and the production of peptide thioesters from bis(2-sulfanylethyl)amido (SEA) peptides. The usefulness of a selected selenol compound is illustrated by the total synthesis of a biologically active human chemotactic protein, which plays an important role in innate and adaptive immunity<br>

scholarly journals Key Vitamin D Target Genes with Functions in the Immune System

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1140 ◽  
Author(s):  
Oona Koivisto ◽  
Andrea Hanel ◽  
Carsten Carlberg
Keyword(s):  
Vitamin D ◽  
Adaptive Immunity ◽  
Vitamin D3 ◽  
Target Genes ◽  
Mononuclear Cells ◽  
Active Form ◽  
Biologically Active ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Innate And Adaptive Immunity

The biologically active form of vitamin D3, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), modulates innate and adaptive immunity via genes regulated by the transcription factor vitamin D receptor (VDR). In order to identify the key vitamin D target genes involved in these processes, transcriptome-wide datasets were compared, which were obtained from a human monocytic cell line (THP-1) and peripheral blood mononuclear cells (PBMCs) treated in vitro by 1,25(OH)2D3, filtered using different approaches, as well as from PBMCs of individuals supplemented with a vitamin D3 bolus. The led to the genes ACVRL1, CAMP, CD14, CD93, CEBPB, FN1, MAPK13, NINJ1, LILRB4, LRRC25, SEMA6B, SRGN, THBD, THEMIS2 and TREM1. Public epigenome- and transcriptome-wide data from THP-1 cells were used to characterize these genes based on the level of their VDR-driven enhancers as well as the level of the dynamics of their mRNA production. Both types of datasets allowed the categorization of the vitamin D target genes into three groups according to their role in (i) acute response to infection, (ii) infection in general and (iii) autoimmunity. In conclusion, 15 genes were identified as major mediators of the action of vitamin D in innate and adaptive immunity and their individual functions are explained based on different gene regulatory scenarios.

scholarly journals Efficient Chemical Protein Synthesis using Fmoc‐Masked N‐Terminal Cysteine in Peptide Thioester Segments

2020 ◽  
Vol 59 (35) ◽  
pp. 14796-14801
Author(s):  
Abhisek Kar ◽  
Jamsad Mannuthodikayil ◽  
Sameer Singh ◽  
Anamika Biswas ◽  
Puneet Dubey ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Chemical Protein Synthesis ◽  
Peptide Thioester

scholarly journals A novel PEG-based solid support enables the synthesis of >50 amino-acid peptide thioesters and the total synthesis of a functional SUMO-1 peptide conjugate

2014 ◽  
Vol 5 (5) ◽  
pp. 2017-2022 ◽  
Author(s):  
Emmanuelle Boll ◽  
Hervé Drobecq ◽  
Nathalie Ollivier ◽  
Laurent Raibaut ◽  
Rémi Desmet ◽  
...  
Keyword(s):  
Amino Acid ◽  
Total Synthesis ◽  
Solid Support ◽  
Amino Acid Peptide ◽  
Peptide Thioester ◽  
Large Peptide ◽  
Peptide Thioesters

Bis(2-sulfanylethyl)amino PEG resin gives access to large peptide thioester segments and to functional SUMO-1 conjugates.

scholarly journals Copper-mediated selenazolidine deprotection enables one-pot chemical synthesis of challenging proteins

2019 ◽  
Author(s):  
Zhenguang Zhao ◽  
Norman Metanis
Keyword(s):  
Protein Synthesis ◽  
Catalytic Activity ◽  
Chemical Synthesis ◽  
Total Synthesis ◽  
Active Site ◽  
Synthetic Approach ◽  
One Pot ◽  
Chemical Protein Synthesis ◽  
Key Technologies ◽  
The One

<p>While chemical protein synthesis (CPS) has granted access to challenging proteins, synthesis of longer proteins is often limited by low abundance or non-strategic placement of cysteine (Cys) residues, essential for native chemical ligations (NCL), as well as multiple purification and isolation steps. Selective deselenization and one-pot CPS serve as key technologies to circumvent these issues. Herein, we describe the one-pot total synthesis of human thiosulfate: glutathione sulfurtransferase (TSTD1), a 115-residue protein with a single Cys residue at its active site, and its seleno-analogue. WT-TSTD1 was synthesized in a C-to-N synthetic approach employing multiple NCL reactions, Cu(II)-mediated deprotection of selenazolidine (Sez), and chemoselective deselenization, all in one-pot. In addition, the protein’s seleno analogue (Se-TSTD1), in which the active site Cys is replaced with selenocysteine, was synthesized with a kinetically controlled ligation in a one-pot, N-to-C synthetic approach. TSTD1’s one-pot synthesis was made possible by the newly reported, rapid, and facile copper-mediated selenazolidine deprotection that can be accomplished in one minute. Finally, catalytic activity of the two proteins indicated that Se-TSTD1 possessed only four-fold lower activity than WT-TSTD1 as a thiosulfate: glutathione sulfurtransferase, suggesting that selenoproteins can have physiologically comparable sulfutransferase activity as their cysteine counterparts. </p>

Efficient Chemical Protein Synthesis using Fmoc‐Masked N‐Terminal Cysteine in Peptide Thioester Segments

2020 ◽  
Vol 132 (35) ◽  
pp. 14906-14911
Author(s):  
Abhisek Kar ◽  
Jamsad Mannuthodikayil ◽  
Sameer Singh ◽  
Anamika Biswas ◽  
Puneet Dubey ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Chemical Protein Synthesis ◽  
Peptide Thioester

Chemical Protein Synthesis Using a Second-Generation N-Acylurea Linker for the Preparation of Peptide-Thioester Precursors

2015 ◽  
Vol 137 (22) ◽  
pp. 7197-7209 ◽  
Author(s):  
Juan B. Blanco-Canosa ◽  
Brunello Nardone ◽  
Fernando Albericio ◽  
Philip E. Dawson
Keyword(s):  
Protein Synthesis ◽  
Second Generation ◽  
Chemical Protein Synthesis ◽  
Peptide Thioester

scholarly journals Copper-mediated selenazolidine deprotection enables one-pot chemical synthesis of challenging proteins

2019 ◽  
Author(s):  
Zhenguang Zhao ◽  
Norman Metanis
Keyword(s):  
Protein Synthesis ◽  
Catalytic Activity ◽  
Chemical Synthesis ◽  
Total Synthesis ◽  
Active Site ◽  
Synthetic Approach ◽  
One Pot ◽  
Chemical Protein Synthesis ◽  
Key Technologies ◽  
The One

<p>While chemical protein synthesis (CPS) has granted access to challenging proteins, synthesis of longer proteins is often limited by low abundance or non-strategic placement of cysteine (Cys) residues, essential for native chemical ligations (NCL), as well as multiple purification and isolation steps. Selective deselenization and one-pot CPS serve as key technologies to circumvent these issues. Herein, we describe the one-pot total synthesis of human thiosulfate: glutathione sulfurtransferase (TSTD1), a 115-residue protein with a single Cys residue at its active site, and its seleno-analogue. WT-TSTD1 was synthesized in a C-to-N synthetic approach employing multiple NCL reactions, Cu(II)-mediated deprotection of selenazolidine (Sez), and chemoselective deselenization, all in one-pot. In addition, the protein’s seleno analogue (Se-TSTD1), in which the active site Cys is replaced with selenocysteine, was synthesized with a kinetically controlled ligation in a one-pot, N-to-C synthetic approach. TSTD1’s one-pot synthesis was made possible by the newly reported, rapid, and facile copper-mediated selenazolidine deprotection that can be accomplished in one minute. Finally, catalytic activity of the two proteins indicated that Se-TSTD1 possessed only four-fold lower activity than WT-TSTD1 as a thiosulfate: glutathione sulfurtransferase, suggesting that selenoproteins can have physiologically comparable sulfutransferase activity as their cysteine counterparts. </p>

Sign in / Sign up

Export Citation Format

Share Document