Retracted Article: Chemical synthesis and antigenic activity of a phosphatidylinositol mannoside epitope from Mycobacterium tuberculosis

Abstract

Phosphatidylinositol mannosides (PIMs) have been investigated as lipidic antigens for a new subunit tuberculosis vaccine. A non-natural diacylated phosphatidylinositol mannoside (Ac₂PIM₂) was designed and synthesized by mimicking the natural PIM₆ processing procedure in dentritic cells. This synthetic Ac₂PIM₂ was achieved from α-methyl D-glucopyranoside 1 in 17 steps in 2.5% overall yield. A key feature of the strategy was extending the use of the chiral myo-inositol building block A to the O-2 and O-6 positions of the inositol unit to allow for introducing the mannose building blocks B1 and B2, and to the O-1 position for the phosphoglycerol building block C. Building block A, being a flexible core unit, may facilitate future access to other higher-order PIM analogues. A preliminary antigenic study showed that the synthetic PIM epitope (Ac₂PIM₂) was significantly more active than natural Ac₂PIM₂, which indicated that the synthetic Ac₂PIM₂ can be strongly immunoactive and may be developed as a potential vaccine.