Fast Protein Modification in the Nanomolar Concentration Range Using an Oxalyl Amide as Latent Thioester**

Snella, Benoît; Grain, Benjamin; Vicogne, Jérôme; Capet, Frédéric; Wiltschi, Birgit; Melnyk, Oleg; Agouridas, Vangelis

doi:10.1002/anie.202204992

Cited by 6 publications

(11 citation statements)

References 34 publications

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“…The deportation of the SEA group from the C-terminal position to the side chain of Asp/Glu is at the price of a reduction of the acyl donor capability due to the increased distance between the electron withdrawing alpha nitrogen and the SEA carbonyl in the Asp/Glu(SEA) systems. Oppositely, the introduction of a strong electron withdrawing group in R as in the oxalyl SEA (oxoSEA) system enabled us to achieve exceptional rates approaching 30 M –1 s –1 , a property that permitted ligation to proceed in the nanomolar range in purified or complex media such a cell lysates …”

Section: Carboxamides As Redox-controlled Latent Thioestersmentioning

confidence: 73%

“…Oppositely, the introduction of a strong electron withdrawing group in R as in the oxalyl SEA (oxoSEA) system enabled us to achieve exceptional rates approaching 30 M –1 s –1 , a property that permitted ligation to proceed in the nanomolar range in purified or complex media such a cell lysates. 4 …”

Section: Carboxamides As Redox-controlled Latent Thioestersmentioning

confidence: 99%

“…Oppositely, the introduction of a strong electron withdrawing group in R as in the oxalyl SEA (oxoSEA) system enabled us to achieve exceptional rates approaching 30 M −1 s −1 , a property that permitted ligation to proceed in the nanomolar range in purified or complex media such a cell lysates. 4 To sum up at this stage, the SEA off amide group discussed above enriches the growing family of latent thioester systems, which include peptide hydrazides 48,49 and some N,S-acyl shift systems 50,51 such as protected cysteinyl prolyl esters 52 or photocaged SEAlide. 53 However, at this stage, the SEA off group appears as a single shot rifle enabling no more than three peptide segments to be assembled in one-pot (see Figure 2).…”

Section: Carboxamides As Redox-controlled Latent Thioestersmentioning

confidence: 99%

“…Int. Chem.2022e202204992 . This study describes the capacity of bis (2-sulfanylethyl) oxalamides (oxoSEA) to act as an efficient acyl donor in the nanomolar concentration range in purified or complex media such as cell lysates.…”

Section: Key Referencesmentioning

confidence: 99%

“…The SEA off amide is extremely stable toward various reagents such as acids, bases, and amine nucleophiles as can be expected for a tertiary carboxamide. Such a property facilitates the installation of a SEA amide group into peptides using standard solid phase or solution protocols. , Also, and as anticipated from the thiol–disulfide interchange equilibrium constants presented in Figure a, SEA off amide 7 is stable in the presence of large excesses of 4-mercaptophenylacetic acid (MPAA), the gold-standard catalyst of NCL, and under conditions that enable the reduction of acyclic disulfides, especially those derived from cysteine. Hence, SEA off amide 7 does not interfere with the NCL reaction using regular thioester components, provided strong reductants are excluded from the ligation mixture.…”

Section: Carboxamides As Redox-controlled Latent Thioestersmentioning

confidence: 99%

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Redox-Controlled Chemical Protein Synthesis: Sundry Shades of Latency

et al. 2022

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Conspectus The last two decades have witnessed the rise in power of chemical protein synthesis to the point where it now constitutes an established corpus of synthetic methods efficiently complementing biological approaches. One factor explaining this spectacular evolution is the emergence of a new class of chemoselective reactions enabling the formation of native peptide bonds between two unprotected peptidic segments, also known as native ligation reactions. In recent years, their application has fueled the production of homogeneous batches of large and highly decorated protein targets with a control of their composition at the atomic level. In doing so, native ligation reactions have provided the means for successful applications in chemical biology, medicinal chemistry, materials science, and nanotechnology research. The native chemical ligation (NCL) reaction has had a major impact on the field by enabling the chemoselective formation of a native peptide bond between a C-terminal peptidyl thioester and an N-terminal cysteinyl peptide. Since its introduction in 1994, the NCL reaction has been made the object of significant improvements and its scope and limitations have been thoroughly investigated. Furthermore, the diversification of peptide segment assembly strategies has been essential to access proteins of increasing complexity and has had to overcome the challenge of controlling the reactivity of ligation partners. One hallmark of NCL is its dependency on thiol reactivity, including for its catalysis. While Nature constantly plays with the redox properties of biological thiols for the regulation of numerous biochemical pathways, such a control of reactivity is challenging to achieve in synthetic organic chemistry and, in particular, for those methods used for assembling peptide segments by chemical ligation. This Account covers the studies conducted by our group in this area. A leading theme of our research has been the conception of controllable acyl donors and cysteine surrogates that place the chemoselective formation of amide bonds by NCL-like reactions under the control of dichalcogenide-based redox systems. The dependency of the redox potential of dichalcogenide bonds on the nature of the chalcogenides involved (S, Se) has appeared as a powerful means for diversifying the systems, while allowing their sequential activation for protein synthesis. Such a control of reactivity mediated by the addition of harmless redox additives has greatly facilitated the modular and efficient preparation of multiple targets of biological relevance. Taken together, these endeavors provide a practical and robust set of methods to address synthetic challenges in chemical protein synthesis.

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Section: Carboxamides As Redox-controlled Latent Thioestersmentioning

confidence: 73%

Section: Carboxamides As Redox-controlled Latent Thioestersmentioning

confidence: 99%

Section: Carboxamides As Redox-controlled Latent Thioestersmentioning

confidence: 99%

Section: Key Referencesmentioning

confidence: 99%

Section: Carboxamides As Redox-controlled Latent Thioestersmentioning

confidence: 99%

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Redox-Controlled Chemical Protein Synthesis: Sundry Shades of Latency

et al. 2022

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Chemical Modification of Peptides and Proteins Using Spirooxindole Oxirane Derivatives

2023

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Methods for chemical modification of proteins and peptides at certain positions are required for the preparation of antibody-drug conjugates, protein-or peptide-biotin conjugates, and conjugates used as therapeutics or as tools in biomedical research. We have developed chemical modification methods that use spirooxindole oxirane derivatives for the synthesis of protein-and peptideconjugates. In most cases, the epoxide group of the spirooxindole oxirane derivatives reacted to form a covalent bond with certain histidine residues and/or the N-terminal amino group of peptides and proteins. The modification reactions of various proteins resulted in the formation of proteins modified at only one or two positions.

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