Functionalization of human serum albumin by tyrosine click

Satsuki Obara, Keita Nakane, Chizu Fujimura, Shusuke Tomoshige, Minoru Ishikawa, Shinichi Sato

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Human serum albumin (HSA) is a promising drug delivery carrier. Although covalent modification of Cys34 is a well-established method, it is desirable to develop a novel covalent modification method that targets residues other than cysteine to introduce multiple functions into a single HSA molecule. We developed a tyrosine-selective modification of HSA. Three tyrosine selective modification methods, hemin-catalyzed, horseradish peroxidase (HRP)-catalyzed, and laccase-cat-alyzed reactions were performed, and the modification efficiencies and modification sites of the modified HSAs obtained by these methods were evaluated and compared. We found that the lac-case-catalyzed method could efficiently modify the tyrosine residue of HSA under mild reaction conditions without inducing oxidative side reactions. An average of 2.2 molecules of functional groups could be introduced to a single molecule of HSA by the laccase method. Binding site analysis using mass spectrometry suggested Y84, Y138, and Y401 as the main modification sites. Further-more, we evaluated binding to ibuprofen and found that, unlike the conventional lysine residue modification, the inhibition of drug binding was minimal. These results suggest that tyrosine-resi-due selective chemical modification is a promising method for covalent drug attachment to HSA.

Original languageEnglish
Article number8676
JournalInternational journal of molecular sciences
Issue number16
Publication statusPublished - 2021 Aug 2


  • Drug binding
  • Human serum albumin
  • Laccase
  • Modification site
  • Tyrosine click

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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