Design, synthesis, and evaluation of β-galactosylceramide mimics promoting β-glucocerebrosidase activity in keratinocytes

We have established an efficient synthesis of mimics of β-galactosylceramide (β-GalCer) increasing a β-glucocerebrosidase (β-GlcCerʹase) activity that associates with the skin barrier function. Among the synthetic β-GalCer analogues (6a–6e) described herein, compound 6e exhibited a potent effect on the activation of β-GlcCerʹase 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.