1-Oxabicyclic beta-lactams as new inhibitors of elongating MPT--a key enzyme responsible for assembly of cell-surface phosphoglycans of Leishmania parasite |
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Authors: | Ruhela Dipali Chatterjee Patrali Vishwakarma Ram A |
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Institution: | Bio-organic Chemistry Lab, National Institute of Immunology, JNU Complex, New Delhi 110-067, India. |
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Abstract: | 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. |
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