Importance of glycosylation in enzyme replacement therapy

Excerpt

Post-translational modification regulates the qualitative and quantitative control of a huge number of proteins in eukaryotes. Multiple sites may be targeted by a wide range of modifications, such as glycosylation, sulphation, methylation, sumoylation, citrullination, farnesylation, biotinylation, ubiquitination and proteolytic cleavage. These complex processes require a multitude of specific enzymes that are species and tissue specific. The subsequent changes modulate the physicochemical properties, folding, conformation, distribution, stability, activity and immunogenicity of the protein. This chapter discusses the post-translational changes of α-galactosidase A and the differences between agalsidase alfa, which is produced in a human cell line (fibroblasts), and agalsidase beta, which is produced in a non-human cell line (Chinese hamster ovary cells). The qualitative and quantitative differences in the post-translational modifications of these glycoproteins may have consequences for the bio-distribution, activity and immunogenic potential of the enzyme.