A sulfonium tethered peptide ligand rapidly and selectively modifies protein cysteine in vicinity

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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Author(s)

  • Dongyuan Wang
  • Mengying Yu
  • Na Liu
  • Chenshan Lian
  • Zhanfeng Hou
  • And 8 others
  • Rui Wang
  • Rongtong Zhao
  • Wenjun Li
  • Yixiang Jiang
  • Xiaodong Shi
  • Shuiming Li
  • Feng Yin
  • Zigang Li

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Detail(s)

Original languageEnglish
Pages (from-to)4966-4972
Journal / PublicationChemical Science
Volume10
Issue number19
Online published25 Mar 2019
Publication statusPublished - 21 May 2019

Link(s)

Abstract

Significant efforts have been invested to develop site-specific protein modification methodologies in the past two decades. In most cases, a reactive moiety was installed onto ligands with the sole purpose of reacting with specific residues in proteins. Herein, we report a unique peptide macrocyclization method via the bis-alkylation between methionine and cysteine to generate cyclic peptides with significantly enhanced stability and cellular uptake. Notably, when the cyclized peptide ligand selectively recognizes its protein target with a proximate cysteine, a rapid nucleophilic substitution could occur between the protein Cys and the sulfonium center on the peptide to form a conjugate. The conjugation reaction is rapid, facile and selective, triggered solely by proximity. The high target specificity is further proved in cell lysate and hints at its further application in activity based protein profiling. This method enhances the peptide's biophysical properties and generates a selective ligand-directed reactive site for protein modification and fulfills multiple purposes by one modification. This proof-of-concept study reveals its potential for further broad biological applications.

Research Area(s)

Citation Format(s)

A sulfonium tethered peptide ligand rapidly and selectively modifies protein cysteine in vicinity. / Wang, Dongyuan; Yu, Mengying; Liu, Na; Lian, Chenshan; Hou, Zhanfeng; Wang, Rui; Zhao, Rongtong; Li, Wenjun; Jiang, Yixiang; Shi, Xiaodong; Li, Shuiming; Yin, Feng; Li, Zigang.

In: Chemical Science, Vol. 10, No. 19, 21.05.2019, p. 4966-4972.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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