Longest Synthetic Oligosialic Acids

Synthetic chains of sialic acids are now available in sizes four times longer than before.

α-Oligosialic acids are found on the surfaces of some pathogenic bacteria and are considered promising components for carbohydrate vaccines that might prime the human immune system to attack deleterious invaders. Synthetic versions could be used in such vaccines and could also help researchers better understand the biological roles of natural α-oligosialic acids, which are found in mammals and on bacteria that cause meningitis, septicemia, and urinary tract infections.

Current vaccines against meningitis and septicemia contain α-oligosialic acids purified from natural sources, which are often heterogeneous in length or contaminated with other antigens—factors that can impair efficacy and cause side effects.

Synthesis could avoid these problems, but until now the longest synthetic α-oligosialic acids have been tetrasaccharides, whereas α-oligosialic acids need eight or more units to be biologically active.

Now, associate research fellow Chung-Yi Wu and President Chi-Huey Wong of Taiwan’s Academia Sinica and coworkers have synthesized pure α-oligosialic acids two, four, six, eight, 10, and 12 units long (Angew. Chem. Int. Ed., DOI: 10.1002/anie.201101794). They succeeded by developing a convergent block synthesis (in which small units are made and joined) with the right protecting group and leaving group to ensure α-only sialylation. “The reagent reported in the paper is the first one with this property,” Wong says. Academia Sinica postdoc Kuo-Ching Chu has already used one of the new α-oligosialic acids to create a candidate vaccine for meningitis and septicemia.

Organic chemist Cristina De Meo of Southern Illinois University, Edwardsville, who specializes in sialic acid synthesis, comments that “building oligosialic acids in high yields and maintaining the desired α-stereoselectivity for every step of the synthesis is an extremely important achievement. This is clearly an important milestone in the synthesis of oligosialic acids that can lead to a better understanding of their biological functions or the design of therapeutics.”