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.
Ruhela
Dipali
D
Bio-organic Chemistry Lab, National Institute of Immunology, JNU Complex, New Delhi 110-067, India.
Chatterjee
Patrali
P
Vishwakarma
Ram A
RA
D000818:Animals; D002236:Carbohydrate Conformation; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006028:Glycosphingolipids / Q000378:metabolism*; D007891:Leishmania / Q000201:enzymology*; D007896:Leishmaniasis / Q000188:drug therapy; D011134:Polysaccharides / Q000737:chemistry*; D017855:Transferases (Other Substituted Phosphate Groups) / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D047090:beta-Lactams / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D006028:Glycosphingolipids; D011134:Polysaccharides; D047090:beta-Lactams; C008290:lipophosphonoglycan; D017855:Transferases (Other Substituted Phosphate Groups); C411542:elongating alpha-D-manosyl phosphosphate transferase