title: Design, synthesis, and evaluation of beta-galactosylceramide mimics promoting beta-glucocerebrosidase activity in keratinocytes.
abstract: We have established an efficient synthesis of mimics of beta-galactosylceramide (beta-GalCer) increasing a beta-glucocerebrosidase (beta-GlcCer'ase) activity that associates with the skin barrier function. Among the synthetic beta-GalCer analogues (6a-6e) described herein, compound 6e exhibited a potent effect on the activation of beta-GlcCer'ase function in vitro and reduced the transepidermal water loss (TEWL) level in a UVB-induced barrier disrupted mice model. These findings indicated that compound 6e could be useful for cosmetics and medicines to improve skin barrier function.
authors.affiliation: Basic Research Laboratory, Kanebo Ltd., 3-28, 5-chome Kotobuki-cho, Odawara-shi, Kanagawa-ken 250-0002, Japan. fukunaga@oda.cos.kanebo.co.jp
authors.forename: Kyoko
authors.initials: K
authors.lastname: Fukunaga
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yoshida
authors.forename: Fumio
authors.initials: F
authors.lastname: Nakajima
authors.forename: Rie
authors.initials: R
authors.lastname: Uematsu
authors.forename: Mariko
authors.initials: M
authors.lastname: Hara
authors.forename: Shintaro
authors.initials: S
authors.lastname: Inoue
authors.forename: Hirosato
authors.initials: H
authors.lastname: Kondo
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Nishimura
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000138:chemical synthesis* / Q000494:pharmacology*; D002478:Cells, Cultured; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D005699:Galactosylceramides / Q000138:chemical synthesis* / Q000494:pharmacology*; D005962:Glucosylceramidase / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000201:enzymology / Q000528:radiation effects; D051379:Mice; D013329:Structure-Activity Relationship; D014466:Ultraviolet Rays; D014870:Water Loss, Insensible / Q000187:drug effects / Q000528:radiation effects
chemical_list: D005699:Galactosylceramides; D005962:Glucosylceramidase