title: Synthesis of photoreactive ivermectin B1a derivatives and their actions on Haemonchus and Bombyx glutamate-gated chloride channels.
abstract: Glutamate-gated chloride channels (GluCls) are inhibitory neurotransmitter receptors that are present only in invertebrates such as nematodes and insects. These channels are important targets of insecticidal, acaricidal, and anthelmintic macrolides such as avermectins, ivermectin (IVM), and milbemycins. To identify the amino acid residues that interact with IVM in GluCls, three IVM B1a derivatives with different photoreactive substitutions at C-13 were synthesized in the present study. These derivatives displayed low- or subnanomolar affinity for parasitic nematode (Haemonchus contortus) and silkworm (Bombyx mori) GluCls expressed in COS-1 cells. The derivatives also activated homomeric H. contortus GluCls expressed in Xenopus oocytes. The results indicate that synthesized photoreactive IVM B1a derivatives have superior affinity and functionality for chemically labeling the macrolide-binding site in GluCls. .
authors.affiliation: Division of Bioscience and Biotechnology, the United Graduate School of Agricultural Sciences, Tottori University, Tottori 680-8553, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Fuse
authors.affiliation: Division of Bioscience and Biotechnology, the United Graduate School of Agricultural Sciences, Tottori University, Tottori 680-8553, Japan; Department of Life Science and Biotechnology, Faculty of Life and Environmental Science, Shimane University, Matsue, Shimane 690-8504, Japan. Electronic address: ikeda@life.shimane-u.ac.jp.
authors.forename: Izumi
authors.initials: I
authors.lastname: Ikeda
authors.affiliation: Department of Life Science and Biotechnology, Faculty of Life and Environmental Science, Shimane University, Matsue, Shimane 690-8504, Japan.
authors.forename: Tomo
authors.initials: T
authors.lastname: Kita
authors.affiliation: Department of Applied Biological Chemistry, Faculty of Agriculture, Kinki University, Nara 631-8505, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Furutani
authors.affiliation: Division of Bioscience and Biotechnology, the United Graduate School of Agricultural Sciences, Tottori University, Tottori 680-8553, Japan; School of Agricultural, Biological and Environmental Sciences, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Nakajima
authors.affiliation: Department of Applied Biological Chemistry, Faculty of Agriculture, Kinki University, Nara 631-8505, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: Department of Life Science and Biotechnology, Faculty of Life and Environmental Science, Shimane University, Matsue, Shimane 690-8504, Japan.
authors.forename: Fumiyo
authors.initials: F
authors.lastname: Ozoe
authors.affiliation: Division of Bioscience and Biotechnology, the United Graduate School of Agricultural Sciences, Tottori University, Tottori 680-8553, Japan; Department of Life Science and Biotechnology, Faculty of Life and Environmental Science, Shimane University, Matsue, Shimane 690-8504, Japan. Electronic address: ozoe-y@life.shimane-u.ac.jp.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Ozoe
mesh_terms: D000818:Animals; D012831:Bombyx; D019556:COS Cells; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D005260:Female; D006189:Haemonchus; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D007559:Ivermectin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D009865:Oocytes / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D018118:Chloride Channels; D015801:Helminth Proteins; D019476:Insect Proteins; C109777:glutamate-gated chloride channels; D007559:Ivermectin
keywords: Bombyx mori; Glutamate-gated chloride channel; Haemonchus contortus; Ivermectin; Photoaffinity labeling; Photoreactive probe