Ultra-rapid Electrophilic Cysteine Arylation

Rapid bond-forming reactions are crucial for efficient bioconjugation. We describe a simple and practical strategy for facilitating ultra-rapid electrophilic cysteine arylation. Using a variety of sulfone-activated pyridinium salts, this uncatalyzed reaction proceeds with exceptionally high rate con...

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Bibliographic Details
Published inJournal of the American Chemical Society Vol. 145; no. 43; pp. 23427 - 23432
Main Authors Lipka, Bradley M., Honeycutt, Daniel S., Bassett, Gregory M., Kowal, Taylor N., Adamczyk, Max, Cartnick, Zachary C., Betti, Vincent M., Goldberg, Jacob M., Wang, Fang
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 01.11.2023
Amer Chemical Soc
Subjects
Chemistry
Chemistry, Multidisciplinary
Cysteine
Peptides
Physical Sciences
Proteins
Science & Technology
CONSTANTS
REAGENTS
REACTIVITY
CHEMISTRY
SULFHYDRYL-GROUPS
PROTEINS
SELECTIVITY
PEPTIDE
PROBES
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Summary:Rapid bond-forming reactions are crucial for efficient bioconjugation. We describe a simple and practical strategy for facilitating ultra-rapid electrophilic cysteine arylation. Using a variety of sulfone-activated pyridinium salts, this uncatalyzed reaction proceeds with exceptionally high rate constants, ranging from 9800 to 320,000 M–1·s–1, in pH 7.0 aqueous buffer at 25 °C. Such reactions allow for stoichiometric bioconjugation of micromolar cysteine within minutes or even seconds. Even though the arylation is extremely fast, the chemistry exhibits excellent selectivity, thus furnishing functionalized peptides and proteins with both high conversion and purity.
Bibliography:ObjectType-Article-1
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ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.3c10334