Cystic fibrosis and diabetes: isoLAB and isoDAB, enantiomeric carbon-branched pyrrolidine iminosugars

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Best, Daniel | Jenkinson, Sarah F | Saville, Waldo, A. | Alonzi, Dominic S | Wormald, Mark R | Butters, Terry, D. | Becq, Frédéric | Norez, Caroline | Blériot, Yves | Adachi, I. | Kato, A. | Fleet, George W J

Edité par CCSD ; Elsevier -

IF : 2,538. International audience. Acetonides are the only protecting groups used in the syntheses of isoDAB from d-ribose and of isoLAB from d-tagatose. isoDAB is a potent and highly specific competitive α-glucosidase inhibitor (for rice α-glucosidase, Ki = 4 μM for isoDAB compared to Ki 14 μM for DAB). isoDAB is not an--whereas DAB is a potent--inhibitor of glycogen phosphorylase. This is the first example of any potent inhibition of glycosidases by a carbon-branched iminosugar pyrrolidine. Although isoLAB shows no inhibition of any glycosidase, preliminary experiments suggest that isoLAB partially rescues the defective F508del-CFTR function and so may have a role in the study of cystic fibrosis.

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