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Detection of Protein S-Acylation using Acyl-Resin Assisted Capture
Published on: April 10, 2020
Residue-Selective C-H Sulfenylation Enabled by Acid-Activated S-Acetamidomethyl Cysteine Sulfoxide with Application
Kento Ohkawachi1, Kaito Anzaki1, Daishiro Kobayashi1
1Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University, Tokushima, 770-8505, Japan.
Abstract:
A tyrosine (Tyr)- or tryptophan (Trp)-selective metal-free C-H sulfenylation reaction using an acid-activated S-acetamidomethyl cysteine (Cys) sulfoxide, Cys(Acm)(O), has been achieved. The dually protonated intermediate produced from Cys(Acm)(O) under acidic conditions allows the sulfenylation of Tyr. Significantly, the reaction in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) mainly affords a Cys-Tyr-linked peptide even in the presence of Trp residues. In contrast, a Cys-Trp-linked peptide was selectively obtained from the reaction in the presence of guanidine hydrochloride (Gn ⋅ HCl) under acidic conditions. Established Tyr- and Trp-selective sulfenylation methods were used in the Cys-Tyr stapling and Trp lipidation of glucagon-like peptides 1 in a one-pot/stepwise manner. Investigation of the mechanism showed that orbital- and charge-controlled reactions are responsible for the Trp and Tyr selectivity, respectively.
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