Chemoselective and photocleavable cysteine modification of peptides and proteins using isoxazoliniums

Jie Ren Deng, Sai Fung Chung, Alan Siu Lun Leung, Wai Ming Yip, Bin Yang, Man Chung Choi, Jian Fang Cui, Karen Ka Yan Kung, Zhen Zhang, Kar Wai Lo, Yun Chung Leung (Corresponding Author), Man Kin Wong (Corresponding Author)

Research output: Journal article publicationJournal articleAcademic researchpeer-review

9 Citations (Scopus)

Abstract

It is of ongoing interest to develop new approaches for efficient and selective modification of cysteine residues on biomolecules. Here we present a comprehensive study on a newly developed isoxazolinium-mediated cysteine modification of peptides and proteins. Using a stoichiometric amount of isoxazolinium reagents generated in situ from a catalytic amount of silver salts, cysteine-containing peptides can be efficiently modified to afford products in nearly complete conversions. With the optimized conditions, free cysteine containing proteins HSA and BSA, as well as a site-directed mutated therapeutic protein (BCArg) can be efficiently and selectively labelled using small amounts of the isoxazolinium reagents. We find that the phenylacyl thioether linkage bearing an alkyne moiety can be rapidly cleaved under irradiation of UV-A light, giving the formation of a thioaldehyde moiety, which can be converted back to cysteine by reduction.

Original languageEnglish
Article number93
JournalCommunications Chemistry
Volume2
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Chemistry
  • Environmental Chemistry
  • Biochemistry

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