Stereoselective Synthesis and Immunological Evaluation of Common O-antigen of P. mirabilis OE and P. vulgaris TG103

Proteus species especially Proteus mirabilis and Proteus vulgaris are zoonotic pathogens which can cause public health disease. Owing to their antibiotic-resistance, developing vaccines against these pathogens is urgently required. Herein, we describe the first synthesis of the common O-antigen of Proteus mirabilis OE and Proteus vulgaris TG 103. The repeating unit incorporates two challenging 1,2-cis-glycosidic bonds: the 1,2-cis-2-acetamido-2-deoxy-glucosidic bonds were successfully constructed by use of conformation-restrained 2-nitroglucal donor under bifunctional organothiourea catalysis; while the 1,2-cis-2-acetamido-2-deoxy-galactosidic bonds were formed by use of di-tert-butylsilylidene protected 2-azidogalactose donors. The synthetic fragments were screened by glycan microarray with immunized rabbit sera against purified LPS from Proteus mirabilis O54. The results revealed that the synthetic common O-antigens both hexasaccharide 2 and nonasaccharide 3 can strongly bind with the IgG antibodies (Abs) in the sera, which is highly valuable for further immunological investigation in synthetic carbohydrate-based vaccine development.