Novel fluorescent ceramide derivatives for probing ceramidase substrate specificity
| Autor: | Denny Proksch, Krishna P. Bhabak, Christoph Arenz, Susanne Redmer |
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| Rok vydání: | 2012 |
| Předmět: |
Ceramide
Clinical Biochemistry Ceramidases Pharmaceutical Science Ceramides Biochemistry Substrate Specificity Structure-Activity Relationship chemistry.chemical_compound Oxazines Drug Discovery Molecular Biology Fluorescent Dyes Neutral Ceramidase Sphingosine Hydrolysis Organic Chemistry Nile red Ceramidase Sphingolipid Acid Ceramidase Kinetics chemistry Molecular Medicine lipids (amino acids peptides and proteins) |
| Zdroj: | Bioorganic & Medicinal Chemistry. 20:6154-6161 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2012.08.035 |
| Popis: | Ceramidases are key regulators of cell fate. The biochemistry of different ceramidases and of their substrate ceramide appears to be complex, mainly due to specific biophysical characteristics at the water-membrane interface. In the present study, we describe the design and synthesis of a set of fluorescently labeled ceramides as substrates for acid and neutral ceramidases. For the first time we have replaced the commonly used polar NBD-dye with the lipophilic Nile Red (NR) dye. Analysis of kinetic data reveal that although both the dyes do not have any noticeable preference for the substitution at acyl or sphingosine (Sph) part in ceramide towards hydrolysis by acid ceramidase, the ceramides with acyl-substituted NBD and Sph-substituted NR dyes have been found to be a better substrate for neutral ceramidase. |
| Databáze: | OpenAIRE |
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