Looking-glass synergistic pharmacological chaperones: DGJ and L-DGJ from the enantiomers of tagatose

Sarah F. Jenkinson; George W.J. Fleet; Robert J. Nash; Yuriko Koike; Isao Adachi; Akihide Yoshihara; Kenji Morimoto; Ken Izumori; Atsushi Kato

doi:10.1021/ol201552q

Looking-glass synergistic pharmacological chaperones: DGJ and L-DGJ from the enantiomers of tagatose

Sarah F. Jenkinson, George W.J. Fleet^*, Robert J. Nash, Yuriko Koike, Isao Adachi, Akihide Yoshihara, Kenji Morimoto, Ken Izumori, Atsushi Kato

^*Corresponding author for this work

Hospital Pharmacy

Research output: Contribution to journal › Article › peer-review

56 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	4064-4067
Number of pages	4
Journal	Organic Letters
Volume	13
Issue number	15
DOIs	https://doi.org/10.1021/ol201552q
State	Published - 2011/08/05

ASJC Scopus subject areas

Biochemistry
Physical and Theoretical Chemistry
Organic Chemistry

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title = "Looking-glass synergistic pharmacological chaperones: DGJ and L-DGJ from the enantiomers of tagatose",

abstract = "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.",

author = "Jenkinson, {Sarah F.} and Fleet, {George W.J.} and Nash, {Robert J.} and Yuriko Koike and Isao Adachi and Akihide Yoshihara and Kenji Morimoto and Ken Izumori and Atsushi Kato",

year = "2011",

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T2 - DGJ and L-DGJ from the enantiomers of tagatose

AU - Jenkinson, Sarah F.

AU - Fleet, George W.J.

AU - Nash, Robert J.

AU - Koike, Yuriko

AU - Adachi, Isao

AU - Yoshihara, Akihide

AU - Morimoto, Kenji

AU - Izumori, Ken

AU - Kato, Atsushi

PY - 2011/8/5

Y1 - 2011/8/5

N2 - 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.

AB - 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.

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JO - Organic Letters

JF - Organic Letters

IS - 15

ER -

Looking-glass synergistic pharmacological chaperones: DGJ and L-DGJ from the enantiomers of tagatose

Abstract

ASJC Scopus subject areas

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