A Sulfonium Triggered Thiol-yne Reaction for Cysteine Modification

Hou, Zhanjun; Wang, Dongyuan; Li, Yang; Zhao, Rongtong; Wan, Chuan; Lian, Chenshan; Yin, Feng; Li, Zigang

doi:10.1021/acs.joc.9b02505

Cited by 23 publications

(30 citation statements)

References 54 publications

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“…These efforts have been extensively reviewed [1–5] . More recently, several more of these methods have been reported that utilize novel functional groups to demonstrate impressive chemoselectivity to Cys, [6–9] Lys, [10–13] His, [14–16] Met, [17–19] Trp, [20] and Tyr [21] …”

Section: Overview Of Protein Modification Methodsmentioning

confidence: 99%

“…These efforts have been extensively reviewed. [1][2][3][4][5] More recently, several more of these methods have been reported that utilize novel functional groups to demonstrate impressive chemoselectivity to Cys, [6][7][8][9] Lys, [10][11][12][13] His, [14][15][16] Met, [17][18][19] Trp, [20] and Tyr. [21] Relatedly, dehydroalanine (Dha)-mediated modification is an indirect but notable approach.…”

Section: Functional Group Innate Reactionsmentioning

confidence: 99%

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Proximity‐driven, Regioselective Chemical Modification of Peptides and Proteins

Hymel

Liu²

2020

Asian J Org Chem

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Chemical methods to covalently modify recombinant peptides and proteins are becoming increasingly valuable as the development of biological therapeutics accelerates. Rapid advances in chemoselectivity have been achieved to modify desired proteogenic and non-proteogenic amino acids. However, regioselectivity, in which a specific amino acid can be modified in the presence of chemically identical residues, has been much more difficult to achieve. This mini-review focuses on recent advances in regioselective chemical modification of peptides and proteins utilizing microenvironment and/or proximity-driven effects to achieve selectivity. While the chemistries and applications involving enzyme active site modification are still being steadily developed, such a concept has also been expanded to the modification of residues

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Section: Overview Of Protein Modification Methodsmentioning

confidence: 99%

Section: Functional Group Innate Reactionsmentioning

confidence: 99%

Proximity‐driven, Regioselective Chemical Modification of Peptides and Proteins

Hymel

Liu²

2020

Asian J Org Chem

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“…133 In the following experiment, Li lab reported another facile thiolyne reaction triggered by sulfonium center and translated it into the synthesis of stapled peptides. 134 The peptide bearing i, i+4 Met-Cys paired residues was used as the linear precursor, which could undergo robust propargylation at Met residue. And then the resulting sulfonium could couple with another Cys residue with satisfying functional group tolerance, thus constructing the stapled peptides with increased serum stability, good GSH resistance, and enhanced cellular uptakes compared to the linear peptides (Scheme 15B).…”

Section: Met-cys Via Chemo-selective Bis-alkylationmentioning

confidence: 99%

“…And then the resulting sulfonium could couple with another Cys residue with satisfying functional group tolerance, thus constructing the stapled peptides with increased serum stability, good GSH resistance, and enhanced cellular uptakes compared to the linear peptides (Scheme 15B). 134 2.9. His-His via Metal Chelates…”

Section: Met-cys Via Chemo-selective Bis-alkylationmentioning

confidence: 99%

Stapled Helical Peptides Bearing Different Anchoring Residues

et al. 2020

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A large proportion of protein–protein interactions (PPIs) occur between a short peptide and a globular protein domain; the peptides involved in surface interactions play important roles, and there is great promise for using peptide motifs to interfere with protein interactions. Peptide inhibitors show more promise in blocking large surface protein interactions compared to small molecule inhibitors. However, peptides have drawbacks including poor stability against circulating proteolytic enzymes and an intrinsic inability to penetrate cell membranes. Stapled helical peptides, by adopting a preformed, stable α-helical conformation, exhibit improved proteolytic stability and membrane permeability compared to linear bioactive peptides. In this review, we summarize the broad aspects of peptide stapling for chemistry, biophysics, and biological applications and specifically highlight the methodology by providing an inventory of different anchoring residues categorized into two natural amino acids, two nonnatural amino acids, or a combination of natural and nonnatural amino acids. Additional advantages of specific peptide stapling techniques, including but not limited to reversibility, bio-orthogonal reactivity, and photoisomerization, are also discussed individually. This review is expected to provide a broad reference for the rational design of druggable stapled peptides targeting therapeutic proteins, particularly those involved in PPIs, by considering the impact of anchoring residues, functional cross-linkers, physical staple length, staple components, and the staple motif on the biophysical properties of the peptides.

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“…On the other hand, thionium is an important intermediate state of Pummerer-type reactions, which is highly active substrates in nucleophilic S E Ar reactions [48][49][50][51][52][53] . Recently, our group developed various sulfonium-based chemistry for bioorthogonal applications with excellent biocompatibility [54][55][56] . Thus, we considered the application of electrophilic thionium intermediates for protein modification.…”

Section: Introductionmentioning

confidence: 99%