Modifications of amino acids using arenediazonium salts

Sengupta, Saumitra; Chandrasekaran, Srinivasan

doi:10.1039/c9ob01471c

Cited by 47 publications

(52 citation statements)

References 209 publications

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“…The resulting products were isolated and triazenation of secondary amines was confirmed by NMR ( 1 H and 13 C) (Supplementary Figure 3). In contrast, no product was observed with alanine, thus reconfirming literature reports that the formation of the triazene‐coupling product with primary amine is reversible in nature (Supplementary Figure 4) [37, 38] …”

Section: Resultssupporting

confidence: 80%

Selective Triazenation Reaction (STaR) of Secondary Amines for Tagging Monomethyl Lysine Post‐Translational Modifications

et al. 2021

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Lysine monomethylation (Kme) is an impactful post‐translational modification (PTM) responsible for regulating biological processes and implicated in diseases, thus there is great interest in identifying these methylation marks globally. However, the progress in this area has been challenging because the addition of a small methyl group on lysine leads to negligible change in the bulk, charge, and hydrophobicity. Herein, we report an empowering chemical technology selective triazenation reaction, which we term “STaR”, of secondary amines using arene diazonium salts to achieve highly selective, rapid, and robust tagging of Kme peptides from a complex mixture under biocompatible conditions. Although the resulting triazene‐linkage with Kme is stable, we highlight the efficient decoupling of the triazene‐conjugate to afford unmodified starting components under mild conditions when desired. Our work establishes a unique chemoselective, traceless bioconjugation strategy for the selective enrichment of Kme PTMs.

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Section: Resultssupporting

confidence: 80%

Selective Triazenation Reaction (STaR) of Secondary Amines for Tagging Monomethyl Lysine Post‐Translational Modifications

et al. 2021

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“…The multimodal reactivity of aryldiazonium salts can be exploited to modify a wide range of amino acids, [63] including Tyr. Aryldiazonium salts, generally prepared from the corresponding anilines by action of a nitrite in a strong acid medium, can establish an azo linkage with the phenol side ring of Tyr by an electrophilic aromatic substitution (Figure 12).…”

Section: Diazonium Coupling Reactionmentioning

confidence: 99%

Tyrosine Conjugation Methods for Protein Labelling

Álvarez-Dorta

Deniaud

Mével

et al. 2020

Chemistry A European J

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Over the last two decades, the development of chemical biology and the need for more defined protein conjugates have fostered active research on new bioconjugation techniques. In particular, a wide range of biorthogonal labelling strategies have been reported to functionalise the phenol side chain of tyrosines (Tyr). Tyr occur at medium frequency and are partially buried at the protein surface, offering interesting opportunities for site-selective labelling of the most reactive residues. Tyr-targeting has proved effective for designing a wide range of important biomolecules including antibody-drug conjugates, fluorescent or radioactive protein probes, glycovaccines, protein aggregates, and PEG conjugates. Innovative methods have also been reported for site-specific labelling with ligand-directed anchors and for the specific affinity capture of proteins. This review will present and discuss these promising alternatives to the conventional labelling of the nucleophilic lysine and cysteine residues.

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“…71,86 In these protocols, the nucleophilic cysteine thiol was modified with organopalladium, organogold reagents, 87 boronic acids, 88 or diazonium salts. 89 As a complementary strategy representing an inverse approach, we envisioned that Ala Sn could be used to introduce aryl (seleno)cysteine with redox-neutral electrophiles such as Nsulfenylsuccinimides 20 or diselenides 21 (Scheme 4B). We found that the cross-coupling of Ala Sn could be catalyzed by in 71% without epimerization at the α-carbonyl.…”

Section: Introductionmentioning

confidence: 99%

Organometallic AlaM Reagents for Umpolung Peptide Diversification

Zhu¹,

Powell²,

Jing³

et al. 2021

Preprint

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Selective modification of peptides and proteins is emerging as a promising strategy to develop novel mechanistic probes and prepare compounds with translational potential. While many methods to perform direct bioconjugation rely on reactions with dehydroalanine, an alternative strategy capitalizing on polarity reversal at the β carbon in amino acids can open access to a new type of diversification reactions characterized by absolute control of regio- and stereoselectivity. Here, we report that alanine carbastannatranes AlaSn can serve as a universal synthon in various C-C and C-heteroatom bond-forming reactions demonstrated in over 50 diverse examples. These reagents are compatible with peptide and protein manipulation techniques and undergo chemoselective conjugation in minutes when promoted by Pd(0). Despite their increased nucleophilicity and propensity to transfer the alkyl group, AlaSn operate at room temperature under buffered conditions (pH 6.5-8.5). We also show that AlaSn can be easily transformed into several canonical L- and D-amino acids in arylation, acylation, and etherification reactions. Furthermore, AlaSn can partake in macrocyclizations exemplified by the synthesis of medium size cyclic peptides with various topologies (7-13 membered macrocycles). Taken together, metalated alanine AlaSn demonstrate unparalleled scope and represent a new type of umpolung reagents suitable for structure-activity relationship studies and peptide diversification.

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Modifications of amino acids using arenediazonium salts

Abstract: Aryl transfer reactions from arenediazonium salts have started to make their impact in chemical biology with initial forays in the arena of arylative modifications and bio-conjugations of amino acids, peptides and proteins.

Cited by 47 publications

References 209 publications

Selective Triazenation Reaction (STaR) of Secondary Amines for Tagging Monomethyl Lysine Post‐Translational Modifications

Selective Triazenation Reaction (STaR) of Secondary Amines for Tagging Monomethyl Lysine Post‐Translational Modifications

Tyrosine Conjugation Methods for Protein Labelling

Organometallic AlaM Reagents for Umpolung Peptide Diversification

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