- Looking-glass synergistic pharmacological chaperones: DGJ and L-DGJ from the enantiomers of tagatose.
Looking-glass synergistic pharmacological chaperones: DGJ and L-DGJ from the enantiomers of tagatose.
Organic letters (2011-07-13)
Sarah F Jenkinson, George W J Fleet, Robert J Nash, Yuriko Koike, Isao Adachi, Akihide Yoshihara, Kenji Morimoto, Ken Izumori, Atsushi Kato
PMID21744786
摘要
The enantiomers of tagatose are converted to L-DGJ [a noncompetitive inhibitor of human lysosome α-galactosidase A (α-Gal A), K(i) 38.5 μM] and DGJ [a competitive inhibitor of α-Gal A, K(i) 15.1 nM] in 66% yield. L-DGJ and DGJ provide the first examples of pharmacological chaperones that (a) are enantiomeric iminosugars and (b) have synergistic activity with implications for the treatment of lysosomal storage disorders and other protein deficiencies.
材料