S‑Protected Cysteine Sulfoxide-Enabled Tryptophan-Selective Modification with Application to Peptide Lipidation

Lipidation of peptides is a promising means of modification that can improve the therapeutic character of biologically active peptides. Here, a novel lipidation protocol for peptides is described. The C–H sulfenylation of indole in peptides using S-p-methoxybenzyl cysteine sulfoxide under acidic con...

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Bibliographic Details
Published in:ACS medicinal chemistry letters 2022-07, Vol.13 (7), p.1125-1130
Main Authors: Kobayashi, Daishiro, Kuraoka, Eisuke, Hayashi, Junya, Yasuda, Takuma, Kohmura, Yutaka, Denda, Masaya, Harada, Norio, Inagaki, Nobuya, Otaka, Akira
Format: Article
Language:English
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Letter
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Summary:Lipidation of peptides is a promising means of modification that can improve the therapeutic character of biologically active peptides. Here, a novel lipidation protocol for peptides is described. The C–H sulfenylation of indole in peptides using S-p-methoxybenzyl cysteine sulfoxide under acidic conditions in the presence of ammonium chloride, anisole, and triisopropylsilane enables late-stage tryptophan-selective peptide lipidation. This developed protocol has been used successfully for the lipidation of glucagon-like peptides. Oral glucose tolerance tests in wild-type mice indicated that the resulting lipidated peptides stimulate insulin secretion and exhibit a more long-lasting blood-glucose-lowering effect than a parent nonlipidated peptide.
ISSN:1948-5875
1948-5875
DOI:10.1021/acsmedchemlett.2c00161