Passport control for glycan maturation: Discovery of a molecular tag that enhances biopharmaceutical quality
A collaborative research group, including researchers from Nagoya City University, National Institutes of Natural Sciences, and RIKEN has uncovered a molecular tool, the "passport sequence," that significantly improves the production efficiency and quality of glycoproteins, such as blood coagulation factor VIII and erythropoietin (EPO).
The work is in the journal iScience. The discovery holds great promise for the development of high-quality biopharmaceuticals.
The study focuses on a short, 10-amino-acid sequence called the "passport sequence," which facilitates the efficient trafficking of glycoproteins through the secretory pathway. When attached to target proteins, this sequence enhances their interactions with glycosylation enzymes in the Golgi apparatus, leading to significantly increased galactosylation and sialylation—critical modifications that impact protein stability and efficacy.
The researchers revealed that the passport sequence selectively interacts with a Golgi protein called NUCB1, which in turn promotes the function of the glycosyltransferase B4GALT1. This mechanism not only improves glycan maturation but also provides a novel strategy for controlling glycosylation in therapeutic glycoproteins, ultimately improving their pharmacokinetics and therapeutic properties.
The researchers say, "This discovery not only offers a new approach to enhancing the production and quality of biopharmaceutical glycoproteins but also provides deeper insights into the complex mechanisms underlying protein glycosylation."
More information: Hirokazu Yagi et al, Molecular tag for promoting N-glycan maturation in the cargo receptor-mediated secretion pathway, iScience (2024).
Journal information: iScience
Provided by Nagoya City University
