Sialic Acid Derivatives, Analogues and Mimetics as Biological Probes and Inhibitors of Sialic Acid Recognizing Proteins
Sialic acids (Sia) are a family of 9-carbon α-keto acids found pre-dominantly at the nonreducing end of oligosaccharide chains on glycoproteins and glycolipids. Sia can occur free in nature, but are generally found glycosidically linked to either galactose (Gal), N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), or as α-(2→8)-linked homopolymers known as polysialic acid (PolySia) (Fig. 11.1). Sia show remarkable structural diversity, with the family currently comprising over 50 naturally occurring members. The larg-est structural variations of naturally occurring Sia are at carbon 5, which can be substituted with either an acetamido, hydroxyacetami-do, or hydroxyl moiety to form 5-N-acetylneuraminic acid (Neu5Ac), 5-N-glycolylneuraminic acid (Neu5Gc), or deaminoneuraminic acids (KDN), respectively (Fig. 11.1), with Neu5Ac being the most common Sia found in nature. Further structural diversity is generated primarily by a combination of the above-mentioned variations at C-5 with modifications of any of the hydroxyl groups located at C-4, C-7, C-8, and C-9. For further information on Sia structure and diversity we highly recommend (Schauer and Kamerling, 1997; Angata and Varki, 2002; Chen and Varki, 2009).