Site-Selective Protein Chemical Modification of Exposed Tyrosine Residues Using Tyrosine Click Reaction

Shinichi Sato, Masaki Matsumura, Tetsuya Kadonosono, Satoshi Abe, Takafumi Ueno, Hiroshi Ueda, Hiroyuki Nakamura, Shinichi Sato, Hiroyuki Nakamura

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Targeting less abundant amino acid residues on the protein surface may realize site-selective protein modification of natural proteins. The relative hydrophobicity of tyrosine combined with the π-πstacking tendency of the aromatic rings results in generally low accessibility. In this study, site-selective protein modification was achieved by targeting surface-exposed tyrosine residues without using a genetic encoding system. Tyrosine residues were modified with N-methylated luminol derivative under single-electron transfer (SET) reaction conditions. Horseradish peroxidase (HRP)-catalyzed SET and electrochemically activated SET modified surface-exposed tyrosine residues selectively. N-Methylated luminol derivative modified tyrosine residues more efficiently than 4-arylurazole under tyrosine click conditions using HRP and electrochemistry. Tyrosine residues that are evolutionarily exposed only in the complementarity-determining region (CDR) of an antibody were selectively modified by tyrosine click reactions. CDR-modified antibodies were applied to in vivo imaging and antibody-drug conjugated (ADC).

Original languageEnglish
Pages (from-to)1417-1424
Number of pages8
JournalBioconjugate chemistry
Volume31
Issue number5
DOIs
Publication statusPublished - 2020 May 20
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

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