Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 438522
Title Assessment of Partially Deoxygenated Deoxynojirimycin Derivates as Glucosylceramide Synthase Inhibitors : Letter
Author(s) Berg, R.J.B.H.N.; Wennekes, T.; Ghisaidoobe, A.; Donker-Koopman, W.E.; Strijland, A.; Boot, R.G.; Marel, G.A. van der; Aerts, J.M.F.G.; Overkleeft, H.S.
Source ACS Medicical Chemistry Letters 2 (2011)7. - ISSN 1948-5875 - p. 519 - 522.
DOI https://doi.org/10.1021/ml200050s
Department(s) Laboratory for Organic Chemistry
VLAG
Publication type Refereed Article in a scientific journal
Publication year 2011
Keyword(s) chiral building-block - glycolipid biosynthesis - insulin sensitivity - nonlysosomal glucosylceramidase - glycosyltransferase inhibitors - 1-deoxynojirimycin derivatives - n-butyldeoxynojirimycin - asymmetric-synthesis - storage disorders - gaucher disease
Abstract Glucosylceramide synthase (GCS) is an approved drug target for the treatment of Gaucher disease and is considered as a valid target for combating other human pathologies, including type 2 diabetes. The clinical drug N-butyldeoxynojirimycin (Zavesca) is thought to inhibit through mimicry of its substrate, ceramide. In this work we demonstrate that, in contrast to what is proposed in this model, the C2-hydroxyl of the deoxynojirimycin core is important for GCS inhibition. Here we show that C6-OH appears of less important, which may set guidelines for the development of GCS inhibitors that have less affinity (in comparison with Zavesca) for other glycoprocessing enzymes, in particular those hydrolases that act on glucosylceramide.
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