NMR STUDIES OF D-ERYTHRO-AND L-THREO-C16-CERAMIDES UNDER PHYSIOLOGICAL CONDITI

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Ceramide itself, or as the lipid backbone of sphingomyelin and glycosphingolipid, is a structural and functional component of cell membranes. Ceramides are involved in the regulation of several cellular processes: differentiation, growth suppression, cell senescence and apoptosis. We have noticed a strong correlation between electronic structure of ceramides and their in vivo and in vitro activity. However, due to poor solubility of ceramides in water, their structure in aqueous solution has never been investigated under physiological conditions. We have overcome this predicament by: (i) mixing ceramide with a selected deuterated cationic surfactant, or (ii) modifying its hydrophobic interface. The purpose of these studies was to develop a universal experimental NMR model system to examine solution structure of naturally occurring ceramides and their unnatural congeners in water at 37C, with pH varied from 4.5 - 8.5. Here we present a first ever set of experimental NMR data showing substantial changes in the structure of D-erythro- and L-threo-C16-ceramides exposed to a different environmental conditions. The dynamics of the system were investigated using T1 relaxation and PFG-NMR diffusion measurements. Current developments are oriented towards ceramide-protein interactions.