For Research Use Only. Not for Clinical Use.

Creative Biolabs is a leading service provider that focuses on half-life extension for drug development. Based on our advanced platforms and extensive experience, now we can provide O-glycosylation half-life extension services for our clients all over the world.

Introduction of Glycosylation and O-GlcNAc

Glycosylation is a common form of post-translational modification that can largely improve the solubility, stability, and pharmacodynamic properties of therapeutic proteins. In humans, more than 50% of all proteins are glycoproteins. Glycosylated proteins or peptides present a variety of functions, such as protein folding regulation, physicochemical properties modulation, immunological properties modification, avoiding proteolytic degradation, mediation of cell-cell and protein-protein interactions, etc. By increasing molecular size, preventing proteolysis, and increasing sialic acid content, the circulatory time of glycosylation proteins can be prolonged.

O-GlcNAc, also known as O-linked GlcNAc or O-linked β-N-acetylglucosamine, is a reversible enzymatic post-translational modification. This modification is characterized by a β-glycosidic bond between the hydroxyl group of the serine or threonine side chain and N-acetylglucosamine (GlcNAc). There are two kinds of enzymes that can be used for the regulation of the O-GlcNAc cycle, including O GlcNAc transferase (OGT) and O-GlcNAcase (OGA).

Features of O-GlcNAc

• O-GlcNAc will not be extended or modified for the formation of more complex glycan structures.
• O-GlcNAc is almost exclusively found on nuclear proteins and cytoplasmic proteins, but not on membrane proteins and secreted proteins.
• O-GlcNAc is a highly dynamic modification and turns over more rapidly than wild-type proteins.

Fig 1. Increasing the negative charge of therapeutic peptides and proteins by the introduction of glycosylation sites or fusion to CTP can also prolong half-life. (Tan, 2018)

Applications of O-glycosylation for Half-Life Extension

Studies have shown that the negatively charged sialic acids present great functions in half-life extension for many glycoproteins with N- or O-glycosylation. Nowadays, chemically well-defined glycosylated biopharmaceuticals can be obtained via synthetic or semisynthetic methods. For example, synthetic erythropoiesis protein (SEP) has been constructed from four peptide fragments to simulate the physical and chemical properties of wild-type EPO glycosylation. Compared with wild-type erythropoietin (EPO), the half-life of SEP after intravenous administration in rats increased by approximately 2 times (from 5.1 hours to 9.5 hours).

Creative Biolabs has been a long-term expert in the field of drug development. As a pioneer and the undisrupted global leader in half-life extension, we offer a variety of solutions to improve your productivity and streamline your research processes. If you are interested in our products or services, please do not hesitate to contact us for more detailed information.

Reference

1. Tan, H.; et al. Recent advances in half-life extension strategies for therapeutic peptides and proteins. Current pharmaceutical design. 2018, 24(41): 4932-4946.