1-Oxabicyclic beta-lactams as new inhibitors of elongating MPT--a key enzyme responsible for assembly of cell-surface phosphoglycans of Leishmania parasite.

New iminosugars (1-oxabicyclic beta-lactam disaccharides) have been synthesized as inhibitors of elongating alpha-D-mannosyl phosphate transferase (eMPT), a key enzyme involved in the iterative biosynthesis of cell-surface phosphoglycans of the Leishmania parasite. The design is based on a transition-state model for this remarkable enzyme that transfers intact alpha-D-mannosyl-phosphate from GDP-Man. Since these phosphoglycans are unique to Leishmania and are essential for its infectivity and survival, their biosynthetic pathway has emerged as a novel target for anti-leishmanial drug and vaccine design.