Application Notes:
This product is the erythro isomer of the glucosylceramide
synthase inhibitor D-threo-PPMP. Whereas D-threo-
PPMP is an active inhibitor both D- and L-erythro-PPMP
are inactive towards glucosylceramide synthase and can
therefore be used for effective comparison studies. 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. It has been
suggested that an accumulation of glucosylceramide may
cause multidrug-resistance in tumor cells and that PPMP
may be useful in reversing or preventing multidrugresistance
by blocking the synthesis of
glucosylceramides.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 Conduritol B epoxide (CBE), an
inhibitor of beta-glucosidase, along with PPMP can be used to create a model of Gaucher disease.4
References:
1. P. Xie et al. “Overexpression of glucosylceramide synthase in associated with multidrug resistance of leukemia cells” Leukemia Research, vol. 32(3) pp.
475-480, 2008
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