scholarly journals A synthetic approach to ‘click’ neoglycoprotein analogues of EPO employing one-pot native chemical ligation and CuAAC chemistry

2019 ◽  
Vol 10 (3) ◽  
pp. 815-828 ◽  
Author(s):  
D. J. Lee ◽  
A. J. Cameron ◽  
T. H. Wright ◽  
P. W. R. Harris ◽  
M. A. Brimble
Keyword(s):  
Native Chemical Ligation ◽  
Synthetic Approach ◽  
One Pot ◽  
Chemical Ligation ◽  
Synthetic Methodologies

The batch-wise variability of commercial erythropoietin (EPO) preparations warrants development of more advanced synthetic methodologies. We have developed a diverse chemical toolkit to prepare ‘click’ neoglycoprotein variants of EPO.

One-pot hydrazide-based native chemical ligation for efficient chemical synthesis and structure determination of toxin Mambalgin-1

2014 ◽  
Vol 50 (44) ◽  
pp. 5837-5839 ◽  
Author(s):  
Man Pan ◽  
Yao He ◽  
Ming Wen ◽  
Fangming Wu ◽  
Demeng Sun ◽  
...  
Keyword(s):  
Chemical Synthesis ◽  
Snake Venom ◽  
Structure Determination ◽  
Native Chemical Ligation ◽  
One Pot ◽  
Chemical Ligation ◽  
Venom Toxin ◽  
Snake Venom Toxin ◽  
Switch Strategy

An efficient one-pot chemical synthesis of snake venom toxin Mambalgin-1 was achieved using an azide-switch strategy combined with hydrazide-based native chemical ligation.

scholarly journals A Straightforward Methodology to Overcome Solubility Challenges for N-Terminal Cysteinyl Peptide Segments Used in Native Chemical Ligation

2020 ◽  
Author(s):  
Skander Abboud ◽  
El hadji Cisse ◽  
Michel Doudeau ◽  
Hélène Bénédetti ◽  
Vincent AUCAGNE
Keyword(s):  
Amino Acids ◽  
Chemical Synthesis ◽  
Building Blocks ◽  
Native Chemical Ligation ◽  
Synthetic Approach ◽  
Chemical Ligation ◽  
Limited Solubility ◽  
Peptide Segments

One of the main limitations encountered during the chemical synthesis of proteins through native chemical ligation (NCL) is the limited solubility of some of the peptide segments. The most commonly used solution to overcome this problem is to derivatize the segment with a temporary solubilizing tag. Conveniently, the tag can be introduced on the thioester segment in such a way that it is removed concomitantly with the NCL reaction. We herein describe a generalization of this approach to N-terminal cysteinyl segment counterparts, using a straightforward synthetic approach that can be easily automated from commercially available building blocks, and applied it to a well-known problematic target, SUMO-2 (93 amino acids).

One-Pot/Sequential Native Chemical Ligation Using Photocaged Crypto-thioester

2016 ◽  
Vol 18 (3) ◽  
pp. 596-599 ◽  
Author(s):  
Keisuke Aihara ◽  
Kosuke Yamaoka ◽  
Naoto Naruse ◽  
Tsubasa Inokuma ◽  
Akira Shigenaga ◽  
...  
Keyword(s):  
Native Chemical Ligation ◽  
One Pot ◽  
Chemical Ligation

scholarly journals Thiazolidine Deprotection by 2-Aminobenzamide-Based Aldehyde Scavenger for One-Pot Multiple Peptide Ligation

2021 ◽  
Author(s):  
Koki Nakatsu ◽  
Hitoshi Murakami ◽  
Gosuke Hayashi ◽  
Akimitsu Okamoto
Keyword(s):  
Native Chemical Ligation ◽  
High Yield ◽  
Side Reactions ◽  
Model Peptide ◽  
One Pot ◽  
Chemical Ligation ◽  
Good Ability ◽  
Synthetic Proteins ◽  
Short Time ◽  
Peptide Ligation

Strategies for one-pot peptide ligation enable chemists to access synthetic proteins at a high yield in a short time. Herein, we report a new one-pot multi-segments ligation strategy using N-terminal thiazolidine (Thz) peptide and a formaldehyde scavenger. Among our designed 2-aminobenzamide-based aldehyde scavengers, 2-amino-5-methoxy-N’,N’-dimethylbenzohydrazide showed a good ability to capture formaldehyde from Thz at pH 4.0. This scavenger had compatibility with the conditions of native chemical ligation at pH 7.5. Using this scavenger for a model peptide ligation system, we performed one-pot four-segment ligation at a high yield without significant side reactions.

Imidazole-Aided Native Chemical Ligation: Imidazole as a One-Pot Desulfurization-Amenable Non-Thiol-Type Alternative to 4-Mercaptophenylacetic Acid

2016 ◽  
Vol 22 (50) ◽  
pp. 17940-17944 ◽  
Author(s):  
Ken Sakamoto ◽  
Shugo Tsuda ◽  
Masayoshi Mochizuki ◽  
Yukie Nohara ◽  
Hideki Nishio ◽  
...  
Keyword(s):  
Native Chemical Ligation ◽  
One Pot ◽  
Chemical Ligation

1,2,4-Triazole-aided native chemical ligation between peptide-N-acyl-N′-methyl-benzimidazolinone and cysteinyl peptide

2017 ◽  
Vol 53 (90) ◽  
pp. 12236-12239 ◽  
Author(s):  
Ken Sakamoto ◽  
Shugo Tsuda ◽  
Hideki Nishio ◽  
Taku Yoshiya
Keyword(s):  
Native Chemical Ligation ◽  
One Pot ◽  
Chemical Ligation

Novel thiol-additive-free NCL using easy-to-prepare peptide-MeNbz and 1,2,4-triazole can be readily combined with one-pot desulfurization and Cys-modification.

scholarly journals Traceless Click-Assisted Native Chemical Ligation Enabled by Protecting Dibenzocyclooctyne from Acid-Mediated Rearrangement with Copper(I)

2020 ◽  
Author(s):  
Patrick Erickson ◽  
James Fulcher ◽  
Michael Kay
Keyword(s):  
Synthetic Peptides ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Ribosomal Subunit ◽  
Side Reaction ◽  
Native Chemical Ligation ◽  
One Pot ◽  
Direct Production ◽  
Chemical Ligation ◽  
Peptide Cleavage

<div><div><div><p>Chemoselective ligation reactions, such as native chemical ligation (NCL), enable the assembly of synthetic peptides into proteins. However, the scope of proteins accessible to total chemical synthesis is limited by ligation efficiency. Sterically hindered thioesters and poorly soluble peptides can undergo incomplete ligations, leading to challenging purifications with low yields. This work describes a new method, ClickAssisted NCL (CAN), which overcomes these barriers. In CAN, peptides are modified with traceless “helping hand” lysine linkers that enable addition of dibenzocyclooctyne (DBCO) and azide handles for strain-promoted alkyne-azide cycloaddition (SPAAC) reactions. This cycloaddition templates the peptides to increase their effective concentration and greatly accelerate ligation kinetics. After ligation, mild hydroxylamine treatment tracelessly removes the linkers to afford the native ligated peptide. Although DBCO is incompatible with standard Fmoc solid-phase peptide synthesis (SPPS) due to an acid-mediated rearrangement that occurs during peptide cleavage, we demonstrate that copper(I) protects DBCO from this side reaction, enabling direct production of DBCO-containing synthetic peptides. Excitingly, low concentrations of triazole-linked model peptides reacted ~1,200-fold faster than predicted for non-templated control ligations, which also accumulated many side products due to the long reaction time. Using the E. coli ribosomal subunit L32 as a model protein, we further demonstrate that the SPAAC, ligation, desulfurization, and linker cleavage steps can be performed in a one-pot fashion. CAN will be useful for overcoming ligation challenges to expand the reach of chemical protein synthesis.</p></div></div></div>

ChemInform Abstract: One-Pot/Sequential Native Chemical Ligation Using N-Sulfanylethylanilide Peptide

ChemInform ◽  
2013 ◽  
Vol 44 (10) ◽  
pp. no-no
Author(s):  
Akira Otaka ◽  
Kohei Sato ◽  
Hao Ding ◽  
Akira Shigenaga
Keyword(s):  
Native Chemical Ligation ◽  
One Pot ◽  
Chemical Ligation
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