Selective modification of alkyne-linked peptides and proteins by cyclometalated gold(III) (C^N) complex-mediated alkynylation

Hok Ming Ko, Jie Ren Deng, Jian Fang Cui, Karen Ka Yan Kung, Yun Chung Leung, Man Kin Wong

Research output: Journal article publicationJournal articleAcademic researchpeer-review

3 Citations (Scopus)

Abstract

Alkyne is a useful functionality incorporated in proteins for site-selective bioconjugation reactions. Although effective bioconjugation reactions such as copper(I)-catalyzed and/or copper-free 1,3-dipolar cycloadditions of alkynes and azides are the most common approaches, the development of new alkyne-based bioconjugation reactions is still an ongoing interest in chemical biology. In this work, a new approach has been developed for selective modification of alkyne-linked peptides and proteins through the formation of arylacetylenes by a cross-coupling reaction of 6-membered ring cyclometalated gold(III) (C^N) complexes (HC^N = 2-arylpyridines) with terminal alkynes. Screening of the reaction conditions with a series of cyclometalated gold(III) complexes with phenylacetylene gave an excellent yield (up to 82%) by conducting the reaction in slightly alkaline aqueous conditions. The reaction scope was expanded to various alkynes, including alkyne-linked peptides to achieve up to >99% conversion. Using fluorescent dansyl (1l) and BODIPY (1m)-linked gold(III) complexes, alkyne-linked lysozyme has been selectively modified.

Original languageEnglish
Article number115375
JournalBioorganic and Medicinal Chemistry
Volume28
Issue number7
DOIs
Publication statusPublished - 1 Apr 2020

Keywords

  • Alkynylation
  • Bioconjugation reaction
  • Gold complexes
  • Protein modification

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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