title: 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.
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.
authors.affiliation: Department of Chemistry, Tohoku University, 6-3 Aramaki-aza Aoba, Aoba-ku, Sendai 980-8578, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Tamura
authors.forename: Sho
authors.initials: S
authors.lastname: Inomata
authors.forename: Makoto
authors.initials: M
authors.lastname: Ebine
authors.forename: Takahisa
authors.initials: T
authors.lastname: Genji
authors.forename: Izumi
authors.initials: I
authors.lastname: Iwakura
authors.forename: Makoto
authors.initials: M
authors.lastname: Mukai
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Shoji
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sugai
authors.forename: Minoru
authors.initials: M
authors.lastname: Ueda
mesh_terms: D000345:Affinity Labels / Q000737:chemistry*; D003517:Cyclopentanes / Q000737:chemistry*; D005960:Glucosides / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008968:Molecular Conformation; D015335:Molecular Probes / Q000737:chemistry*; D054883:Oxylipins / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D012995:Solubility; D014230:Triazoles / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D000345:Affinity Labels; D003517:Cyclopentanes; D005960:Glucosides; D015335:Molecular Probes; D054883:Oxylipins; D011506:Proteins; D014230:Triazoles; D014867:Water; C011006:jasmonic acid