Triazoyl-phenyl linker system enhancing the aqueous solubility of a molecular probe and its efficiency in affinity labeling of a target protein for jasmonate glucoside

Satoru Tamura, Sho Inomata, Makoto Ebine, Takahisa Genji, Izumi Iwakura, Makoto Mukai, Mitsuru Shoji, Takeshi Sugai, Minoru Ueda

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

In methods employing molecular probes to explore the targets of bioactive small molecules, long or rigid linker moieties are thought to be critical factors for efficient tagging of target protein. We previously reported the synthesis of a jasmonate glucoside probe with a highly rigid linker consisting of a triazoyl-phenyl (TAzP) moiety, and this probe demonstrated effective target tagging. Here we compare the TAzP probe with other rigid or flexible probes with respect to target tagging efficiency, hydrophobic parameters, aqueous solubility, and dihedral angles around the biaryl linkage by a combination of empirical and calculation methods. The rigid biaryl linkage of the TAzP probe has a skewed conformation that influences its aqueous solubility. Such features that include rigidness and good aqueous solubility resulted in highly efficient target tagging. These findings provide a promising guideline toward designing of better linkers for improving molecular probe performance.

Original languageEnglish
Pages (from-to)188-193
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume23
Issue number1
DOIs
Publication statusPublished - 2013 Jan 1

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Keywords

  • CuAAC
  • Linker
  • Molecular probe
  • TAzP
  • Target protein

ASJC Scopus subject areas

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

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