Looking-Glass Synergistic Pharmacological Chaperones: DGJ and L-DGJ from the Enantiomers of Tagatose

被引：53
作者：
Jenkinson, Sarah F. [1 ,2 ]
Fleet, George W. J. [1 ,2 ]
Nash, Robert J. [3 ]
Koike, Yuriko [4 ]
Adachi, Isao [4 ]
Yoshihara, Akihide [5 ]
Morimoto, Kenji [5 ]
Izumori, Ken [5 ]
Kato, Atsushi [4 ]
机构：
[1] Univ Oxford, Chem Res Lab, Dept Chem, Oxford OX1 3TA, England
[2] Univ Oxford, Oxford Glycobiol Inst, Oxford OX1 3QU, England
[3] Phytoquest Ltd, Plas Gogerddan Aberystwyth, Aberystwyth SY23 3EB, Ceredigion, Wales
[4] Toyama Univ, Dept Hosp Pharm, Toyama 9300194, Japan
[5] Kagawa Univ, Rare Sugar Res Ctr, Miki, Kagawa 7610795, Japan
来源：
ORGANIC LETTERS | 2011年 / 13卷 / 15期
关键词：
LYSOSOMAL ALPHA-GALACTOSIDASE; CYSTIC-FIBROSIS; GLYCOSIDASE INHIBITORS; BIOLOGICAL EVALUATION; FABRY LYMPHOBLASTS; NATURAL OCCURRENCE; TAY-SACHS; L-PSICOSE; L-DMDP; MIGLUSTAT;
D O I：
10.1021/ol201552q
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
The enantiomers of tagatose are converted to L-DGJ [a noncompetitive inhibitor of human lysosome alpha-galactosidase A (alpha-Gal A), K-i 38.5 mu M] and DGJ [a competitive inhibitor of alpha-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.
引用
收藏
页码：4064 / 4067
页数：4
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