Sialic Acids are most often found at the terminal position of glycans, and therefore are a likely point of contact for glycan-ligand interactions.
Biopharmaceutical sialylation refers to the type and distribution of sialic acids in the glycans of therapeutic glycoproteins. Sialylation can significantly influence the safety and efficacy profiles of these drugs. In particular, the in vivo half-life of some biopharmaceuticals correlates with the degree of oligosaccharide sialylation.
Furthermore, the sialylation pattern can be a very useful measure of product consistency during manufacturing. Advances in our understanding of these issues have led the FDA, EMEA and other regulators to tighten their rules on glycoprofiling throughout the drug life cycle.
The two main types of sialyl residues found in biopharmaceuticals produced in mammalian expression systems are N-acetyl-neuraminic acid (NeuAc) and N-glycolylneuraminic acid (NeuGc). These usually occur as terminal structures attached to galactose (Gal) residues at the non-reducing terminii of both N- and O-linked glycans.
Controlling the ratio of NeuAc to NeuGc is critical for biomanufacturers. The reason is that NeuAc is the desired, normal human-type sialylation, while NeuGc is found in non-human glycoproteins and is considered an undesired, aberrant form of sialylation for therapeutic glycoproteins.