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Cystic fibrosis and diabetes: isoLAB and isoDAB, enantiomeric carbon-branched pyrrolidine iminosugars |
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| Authors: | Daniel Best A Waldo Saville Mark R Wormald Caroline Norez Yves Blériot Atsushi Kato |
| Institution: | a Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK b Department of Hospital Pharmacy, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan c Oxford Glycobiology Institute, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK d Institut de Physiologie et Biologie Cellulaires, Université de Poitiers, CNRS, 40 avenue du Recteur Pineau, 86022 Poitiers, France e Laboratoire de Synthèse et Réactivité des Substances Naturelles, UMR 6514, 40 avenue du Recteur Pineau, 86022 Poitiers, France |
| Abstract: | 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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