Glycosylation of Therapeutic Proteins

Abstract

During their development and administration, protein-based drugs routinely display suboptimum therapeutic efficacies due to their poor physicochemical and pharmacological properties. These innate liabilities have driven the development of molecular level strategies to improve the therapeutic behavior of protein drugs. Among, the currently developed approaches, glycoengineering is one of the most promising due fact that it has been shown to simultaneously afford improvements over most of the parameters necessary for optimization of protein drug in vivo efficacy (e.g., in vitro and in vivo molecular stability, pharmacodynamic responses, and pharmacokinetic profiles) while allowing for targeting to the desired site of action. The intent of this article is to provide an account of the effects that glycosylation has on the therapeutic efficacy of protein drugs and to describe the current understanding of the mechanisms by which glycosylation leads to such effects.

Post-translational add-ons mark the path in exosomal protein sorting

“…Moreover, addition of a C-t ubiquitin or SUMO tag could deliver proteins into exosomes, including targeting-peptides-LAMP2 with glycosylated motifs for specific tissue delivery [106,137,142]. Besides, protein glycosylation has improved the efficacy of therapeutic proteins [143]. Thus, addition of glycosylating motifs to the protein of interest could also mediate its incorporation to exosomes, although protein glycosylation is still technically complex for industrial production [73,107] (Fig.…”

Assessment of the Effects of Glycosylation on the Pattern and Kinetics of Degradation of Lenograstim in Comparison to Filgrastim Using a Stability-Indicating Orthogonal Testing Protocol

“…Recently developed products have been "engineered" to overcome the above-mentioned limitations, extend the duration of action and reduce immunogenicity. Glycosylation is the most common form of posttranslational modifications in eukaryotes and has been widely employed in biopharmaceutical industry [5][6][7][8]. However, the complexity and variability of glycosylation among different expression systems required in-depth evaluation and monitoring of the quality attributes of glycosylated biopharmaceuticals [5,8].…”

Direct Site-Specific Glycoform Identification and Quantitative Comparison of Glycoprotein Therapeutics: Imiglucerase and Velaglucerase Alfa

“…The glycoforms of therapeutic glycoproteins can potentially contribute to their efficacy, stability, and safety (15)(16)(17)(18)(19)(20)(21)(22). Specifically, acidic glycans containing sialic acid, sulfate, or phosphate have well-known structural properties with specific functional roles in biological processes involving cellular uptake, elimination, and immunogenicity (23,24).…”