Application Notes:
This product is a glucosylceramide synthase inhibitor, an
enzyme that is essential for the synthesis of a very large
number of different glycolipids that are found in many
organisms. PPMP has four possible isomers due to its two
chiral centers (D-threo, L-threo, D-erythro, and L-erythro).
Due to PPMP’s ability to inhibit the joining of ceramides
with carbohydrates there can be an accumulation of
ceramide in the cells and this can lead to apoptosis. This
process has been suggested as a treatment for cancer since
the addition of agents that retard ceramide glucosylation,
such as PPMP, have been shown to increase cytotoxicity in
tumor cells.1 Cells that were incubated with PPMP have
been shown to have a 50% decrease in the viral fusion of
HIV-1, causing a reduction in the penetration of this virus
into these cells.2 PPMP has been used to arrest the growth of
the malarial causing parasite Plasmodium falciparum by inhibiting its very specific glucosylceramide synthase, an approach
that has great potential for malarial chemotherapy.3 In addition to its stereochemistry, the acyl chain of PPMP has a very
marked effect on the intensity of the inhibitory action of the molecule. Conduritol beta epoxide (CBE), an inhibitor of betaglucosidase,
and PPMP, an inhibitor of glucosylceramide synthase, can be used to create a model of Gaucher disease.4
References:
1. B. Maurer et al. “Synergistic Cytotoxicity in Solid Tumor Cell Lines Between N-(4-Hydroxyphenyl)retinamide and Modulators of Ceramide Metabolism”
Journal of the National Cancer Institute, Vol. 92(23) pp. 1897-1909, 2000
2. A. Puri et al. “Human Erythrocyte Glycolipids Promote HIV-1 Envelope Glycoprotein-Mediated Fusion of CD4+Cells” Biochemical and Biophysical
Research Communications, Vol. 242 pp. 219-225, 1998
3. A. Couto et al. “Glycosphingolipids in Plasmodium falciparum: Presence of an active glucosylceramide synthase” European Journal of Biochemistry,
Vol. 271 pp. 2204-2214, 2004
4. D. Sillance et al. “Glucosylceramide modulates membrane traffic along the endocytic pathway” Journal of Lipid Research, Vol. 43 pp. 1837-1845, 2002