Chemical synthesis and antigenic activity of a phosphatidylinositol mannoside epitope from Mycobacterium tuberculosis. Issue 90 (26th October 2020)

• Record Type: Journal Article
• Authors: Zhao, Shi-Yuan; Li, Na; Luo, Wan-Yue; Zhang, Nan-Nan; Zhou, Rong-Ye; Li, Chen-Yu; Wang, Jin
• Is Part Of: Chemical communications. Volume 56:Issue 90(2020)
• Page Start: 14067
• Page End: 14070
• Publication Date: 2020-10-26
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1039/d0cc05573e
• Languages: English
• ISSNs: 1359-7345

Abstract

Abstract : Non-natural PIM epitope Ac2 PIM2 was presented by CD1b to active T cell to release IFN-γ. Abstract : Phosphatidylinositol mannosides (PIMs) have been investigated as lipidic antigens for a new subunit tuberculosis vaccine. A non-natural diacylated phosphatidylinositol mannoside (Ac2 PIM2 ) was designed and synthesized by mimicking the natural PIM6 processing procedure in dentritic cells. This synthetic Ac2 PIM2 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 (Ac2 PIM2 ) was significantly more active than natural Ac2 PIM2, which indicated that the synthetic Ac2 PIM2 can be strongly immunoactive and may be developed as a potential vaccine.