Novel Inhibitors of the acid and neutral ceramidases

The sphingolipid ceramide is a signalling substance, which can be released e.g. from sphingomyelin by the action of different sphingomyelinases in response to extra- or intracellular stimuli. Ceramide triggers antimitogenic effects such as cell-cycle arrest, cell differentiation and programmed cell death (apoptosis) in a variety of cell lines. Degradation of ceramide is catalysed by various ceramidases, which together with sphingomyelinases adjust cellular ceramide concentrations. Small-molecule inhibitors of ceramidases are able to prevent tumour growth in various model systems. Not least because of the low potency of the available ceramidase inhibitors and because of the very laborious measures of sphingolipid turnover in living cells, many questions concerning ceramide-mediated signalling still remain open. We want to synthesize novel fluorescent probes allowing a spatially resolved monitoring of ceramidase and sphingomyelinase activities in living cells in real-time. Such probes might enable visualization of how sphingomyelinases and ceramidases act together in order to adjust cellular ceramide levels. Our second task is to develop new inhibitors for the various ceramidases. Because they are rationally designed, we are confident the envisioned inhibitors would be more potent and more specific than existing ones.

Principal Investigators
Arenz, Christoph Prof. Dr. (Details) (Organic Synthesis)

Financer
DFG: Sachbeihilfe

Duration of Project
Start date: 09/2010
End date: 08/2013

Last updated on 2020-01-06 at 18:52