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

Fingerprint

Molecular Probes
Glucosides
Solubility
Labeling
Proteins
Guidelines
Dihedral angle
Conformations
jasmonic acid
Molecules

Keywords

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

ASJC Scopus subject areas

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

Cite this

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

In: Bioorganic and Medicinal Chemistry Letters, Vol. 23, No. 1, 01.01.2013, p. 188-193.

Research output: Contribution to journalArticle

Tamura, Satoru ; Inomata, Sho ; Ebine, Makoto ; Genji, Takahisa ; Iwakura, Izumi ; Mukai, Makoto ; Shoji, Mitsuru ; Sugai, Takeshi ; Ueda, Minoru. / 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. In: Bioorganic and Medicinal Chemistry Letters. 2013 ; Vol. 23, No. 1. pp. 188-193.
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