A statistical view of protein chemical synthesis using NCL and extended methodologies

Agouridas, Vangelis; Mahdi, Ouafâa El; Cargoët, Marine; Melnyk, Oleg

doi:10.1016/j.bmc.2017.05.050

Cited by 63 publications

(76 citation statements)

References 63 publications

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“…SUMO-2/3 dimers are composed of 183-185 amino acid residues and as such represent the largest proteins produced so far using N,S-acyl shift thioester surrogates. 50,51…”

Section: Assembly Of Sumo-2/3 Dimersmentioning

confidence: 99%

Total Chemical Synthesis of All SUMO-2/3 Dimer Combinations

et al. 2019

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One hallmark of protein chemical synthesis is its capacity to access proteins that living systems can hardly produce. This is typically the case for proteins harboring post-traductional modifications such as ubiquitin or ubiquitin-like modifiers. Various methods have been developed for accessing polyubiquitin conjugates by semi or total synthesis. Comparatively, the preparation of small-ubiquitin like modifier (SUMO) conjugates and more particularly of polySUMO scaffolds is much less developed. We describe hereinafter a synthetic strategy for accessing all SUMO-2/3 dimer combinations.

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“…SUMO-2/3 dimers are composed of 183-185 amino acid residues and as such represent the largest proteins produced so far using N,S-acyl shift thioester surrogates. 50,51…”

Section: Assembly Of Sumo-2/3 Dimersmentioning

confidence: 99%

Total Chemical Synthesis of All SUMO-2/3 Dimer Combinations

et al. 2019

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“…Cys and Lys residues offer the advantage of the nucleophilic thiol and amine side-chain functional groups and their use in such modifications has been reviewed (Boutureira and Bernardes, 2015;Gunnoo and Madder, 2016). Cys residues, in particular, have a relatively low frequency of occurrence in naturally occurring sequences, at 1.48% (Agouridas et al, 2017). Development of an arsenal of varied and specific methodologies for peptide modification allows chemoselective targeting of specific residues or functional groups and is therefore of utmost importance in peptide science.…”

Section: Introductionmentioning

confidence: 99%

Applications of Thiol-Ene Chemistry for Peptide Science

Nolan

Scanlan

2020

Front. Chem.

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Radical thiol-ene chemistry has been demonstrated for a range of applications in peptide science, including macrocyclization, glycosylation and lipidation amongst a myriad of others. The thiol-ene reaction offers a number of advantages in this area, primarily those characteristic of “click” reactions. This provides a chemical approach to peptide modification that is compatible with aqueous conditions with high orthogonality and functional group tolerance. Additionally, the use of a chemical approach for peptide modification affords homogeneous peptides, compared to heterogeneous mixtures often obtained through biological methods. In addition to peptide modification, thiol-ene chemistry has been applied in novel approaches to biological studies through synthesis of mimetics and use in development of probes. This review will cover the range of applications of the radical-mediated thiol-ene reaction in peptide and protein science.

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“…One limitation of NCL is the low reactivity of peptide thioesters containing C-terminal threonine (Thr, T), valine (Val, V), isoleucine (Ile, I), or proline (Pro, P) residues (Fig. 1a ) 18 , which is reflected by the reluctance of peptide chemists to produce linear or cyclic peptides through the formation of such difficult junctions 19 . Therefore, the search for simple and fast ligation methods is a timely and significant goal that should streamline the production of complex peptides including cyclic architectures 20 , 21 .…”

Section: Introductionmentioning

confidence: 99%

Accelerated microfluidic native chemical ligation at difficult amino acids toward cyclic peptides

Ollivier¹,

Toupy²,

Hartkoorn³

et al. 2018

Nat Commun

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Cyclic peptide-based therapeutics have a promising growth forecast that justifies the development of microfluidic systems dedicated to their production, in phase with the actual transitioning toward continuous flow and microfluidic technologies for pharmaceutical production. The application of the most popular method for peptide cyclization in water, i.e., native chemical ligation, under microfluidic conditions is still unexplored. Herein, we report a general strategy for fast and efficient peptide cyclization using native chemical ligation under homogeneous microfluidic conditions. The strategy relies on a multistep sequence that concatenates the formation of highly reactive S-(2-((2-sulfanylethyl)amino)ethyl) peptidyl thioesters from stable peptide amide precursors with an intramolecular ligation step. With very fast ligation rates (<5 min), even for the most difficult junctions (including threonine, valine, isoleucine, or proline), this technology opens the door toward the scale-independent, expedient preparation of bioactive macrocyclic peptides.

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A statistical view of protein chemical synthesis using NCL and extended methodologies

Cited by 63 publications

References 63 publications

Total Chemical Synthesis of All SUMO-2/3 Dimer Combinations

Total Chemical Synthesis of All SUMO-2/3 Dimer Combinations

Applications of Thiol-Ene Chemistry for Peptide Science

Accelerated microfluidic native chemical ligation at difficult amino acids toward cyclic peptides

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