Synthetic and Immunological Studies of Mycobacterial Lipoarabinomannan Oligosaccharides and Their Protein Conjugates

The Journal of Organic Chemistry
Lizhen WangZhongwu Guo

Abstract

Lipoarabinomannan (LAM) is one of the major constituents of the Mycobacterium tuberculosis cell wall and an attractive molecular scaffold for antituberculosis drug and vaccine development. In this paper, a convergent strategy was developed for the synthesis of LAM oligosaccharides with an α-1,2-linked dimannopyranose cap at the nonreducing end. The strategy was highlighted by efficient coupling of separately prepared nonreducing end and reducing end oligosaccharides. Glycosylations were mainly achieved with thioglycoside donors, which gave excellent yields and stereoselectivity even for reactions between complex oligosaccharides. The strategy was utilized to successfully synthesize tetra-, hepta-, and undecasaccharides of LAM from d-arabinose in 10, 15, and 14 longest linear steps and 7.84, 7.50, and 2.59% overall yields, respectively. The resultant oligosaccharides with a free amino group at their reducing end were effectively conjugated with carrier proteins, including bovine serum albumin and keyhole limpet hemocyanin (KLH), via a bifunctional linker. Preliminary immunological studies on the KLH conjugates revealed that they could elicit robust antibody responses in mice and that the antigen structure had some influence on t...Continue Reading

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Citations

Oct 29, 2015·The Journal of Organic Chemistry·Kamar Sahloul, Todd L Lowary
Jun 14, 2016·Accounts of Chemical Research·Todd L Lowary
Jul 7, 2017·The Journal of Organic Chemistry·Harin LeelayuwapanSiwarutt Boonyarattanakalin
Oct 2, 2019·Frontiers in Immunology·Margarida Correia-NevesGunilla Källenius
Jul 18, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Cinzia ColomboLuigi Lay
Jun 20, 2017·Chembiochem : a European Journal of Chemical Biology·Maciej A Walczak, Feng Zhu
Apr 11, 2020·Beilstein Journal of Nanotechnology·Gennady L BuryginLev A Dykman
Mar 9, 2021·Frontiers in Immunology·Willemijn F RijninkSimone A Joosten
Jul 28, 2020·European Journal of Medicinal Chemistry·Zhihao LiYongmin Zhang

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