Mathematisch-Naturwissenschaftliche Fakultät - Jahrgang 2008

Titel

Synthesis and analysis of conformationally restricted ceramide analogs
(Synthese und Untersuchung konformativ fixierter Ceramidanaloga)

Autor

Jennifer Wirtz

Publikationsform

Dissertation

Abstract

Ceramide (e.g. (2S,3R,4E)-2-Octadecanoylamino-octadec-4-en-1,3-diol) is a structural component of membrane glycosphingolipids and sphingomyelin, and occurs in free form as well as bound to proteins in the human skin (Kolter and Sandhoff, 1999). Certain conformationally rigid analogs of this lipid, such as 5b and 24, showed an unexpected interference with the biosynthesis of complex glycosphingolipids such as that of ganglioside GM2 (GalNAcβ1,4-(NeuAcα2,3)Galβ1,4Glcβ1Cer; Figure 1.2).
To get insight into the molecular mechanism of this apparent inhibition, a series of experiments have been carried out in this work:
1) New structural analogs of the halogenated oxazinanone (5a) and oxazolidinone (5b) have been prepared, and analysed in cultured cells.
1a) The preparative route that gave access to these compounds was used for the preparation of the brominated compounds 7.2a and 7.2b. At least in cultured fibroblasts, the biosynthetic incorporation of 3-[14C]L-serine into cellular glycosphingolipids in the presence of 5b and 7.2b were similar. more...

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