Abstract:
Polysialic acid (polySia) is a potent immunomodulatory glycan found on the majority of leukocytes. It consists of a long homopolymer of up to 400 α2,8-linked sialic acid residues and is only found on a limited number of glycoproteins. Like many other sialic acids, polySia acts as an immune checkpoint in that it attenuates the immune response. However, the mechanisms by which it acts remain poorly understood, in large part due to the lack of tools with which to study it. Investigating polySia poses some novel challenges as it is a long, acidic polysaccharide that is also acid and temperature-labile. We have developed new chemical biology tools that allow us to identify polySia-containing proteins, quantify polySia and the proteins to which it is attached, and inhibit the formation of polySia in live cells. These tools have led to new discoveries of the role of polySia in immunology.