Advances in the biology and chemistry of sialic acids

Abstract

Sialic acids are a subset of nonulosonic acids, which are nine-carbon alpha-keto aldonic acids. Natural existing sialic acid-containing structures are presented in different sialic acid forms, various sialyl linkages, and on diverse underlying glycans. They play important roles in biological, pathological, and immunological processes. Sialobiology has been a challenging and yet attractive research area. Recent advances in chemical and chemoenzymatic synthesis, as well as large-scale E. coli cell-based production, have provided a large library of sialoside standards and derivatives in amounts sufficient for structure-activity relationship studies. Sialoglycan microarrays provide an efficient platform for quick identification of preferred ligands for sialic acid-binding proteins. Future research on sialic acid will continue to be at the interface of chemistry and biology. Research efforts not only will lead to a better understanding of the biological and pathological importance of sialic acids and their diversity but also could lead to the development of therapeutics.

Figure 1

Naturally existing sialic acids (a–c) and some other common nonulosonic acids (d and e). Many possible modifications and sialosidic linkage varieties found in nature are not shown here (see references –7).

Figure 2

Sialyl donors used in recent chemical sialylation reactions.

Figure 3

Sialosides containing 12 naturally occurring sialic acid forms (13–24) that have been synthesized from sialic acid precursors (1–12) using a one-pot three-enzyme system.