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Synthesis of Isofagomine Derivatives as New Fluorescence pH Indicators/Glycosidase Inhibitors
Author(s) -
Wang Bo,
Bogh Sidsel Ammitzbøll,
Poulsen Jens Christian Navarro,
Laursen Bo W.,
Bols Mikael
Publication year - 2020
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202000522
Subject(s) - chemistry , fluorescence , stereochemistry , alkyl , amine gas treating , protonation , enzyme , organic chemistry , ion , physics , quantum mechanics
Inhibitor protonation of azasugars of the isofagomine type when bound to enzyme can be investigated using photon induced electron transfer (PET) quenching of an attached fluorophore. For this purpose, Isofagomine, iso‐ d ‐ galacto ‐fagomine, and iso‐ l ‐ gulo ‐fagomine were converted to N ‐(10‐chloroanthracenenyl‐9‐alkyl) derivatives where the alkyl group contained one, two, or three methylene groups. The new derivatives displayed pH dependent fluorescence; as the ammonium forms they were fluorescent, while 90–99 % of the fluorescence was quenched in the amine forms. The 3 isofagomine derivatives were competitive inhibitors of T. Maritima Ι‐glucosidase with K i values from 0.37–4.6ΤM. Similarly, the iso‐ d ‐ galacto ‐fagomines inhibited A. Niger Ι‐galactosidase with K i values from 63–2000 n m . When bound to the enzymes the inhibitors displayed between 1–15 % fluorescence.