Increasing the sialylation of therapeutic glycoproteins: The potential of the sialic acid biosynthetic pathway

Bork, Kaya; Horstkorte, Rüdiger; Weidemann, Wenke

doi:10.1002/jps.21684

Cited by 154 publications

(122 citation statements)

References 87 publications

(90 reference statements)

Supporting

Mentioning

116

Contrasting

Unclassified

Order By: Relevance

“…These can interact with glycoreceptors of liver cells, including the asialoglycoprotein receptor, which recognizes terminal galactose and Nacetylgalactosamine residues (60). Thus, the absence of terminal sialic acid residues can result in a decreased half-life of a glycoprotein (61).…”

Section: Influence Of Fab Glycosylation On Igg Functionmentioning

confidence: 99%

The Emerging Importance of IgG Fab Glycosylation in Immunity

Bovenkamp

Hafkenscheid

Rispens

et al. 2016

The Journal of Immunology

248

216

View full text Add to dashboard Cite

Human IgG is the most abundant glycoprotein in serum and is crucial for protective immunity. In addition to conserved IgG Fc glycans, ∼15–25% of serum IgG contains glycans within the variable domains. These so-called “Fab glycans” are primarily highly processed complex-type biantennary N-glycans linked to N-glycosylation sites that emerge during somatic hypermutation. Specific patterns of Fab glycosylation are concurrent with physiological and pathological conditions, such as pregnancy and rheumatoid arthritis. With respect to function, Fab glycosylation can significantly affect stability, half-life, and binding characteristics of Abs and BCRs. Moreover, Fab glycans are associated with the anti-inflammatory activity of IVIgs. Consequently, IgG Fab glycosylation appears to be an important, yet poorly understood, process that modulates immunity.

show abstract

Section: Influence Of Fab Glycosylation On Igg Functionmentioning

confidence: 99%

The Emerging Importance of IgG Fab Glycosylation in Immunity

Bovenkamp

Hafkenscheid

Rispens

et al. 2016

The Journal of Immunology

248

216

View full text Add to dashboard Cite

show abstract

“…These are organic compounds, composed of protein as well as carbohydrate monosaccharides, usually hexose, hexosamine, fucose and sialic acid, joined together covalently linked to polypeptide chain. The level of different types of serum glycoproteins are maintained within a narrow range in health [10], but is elevated in many pathological conditions viz. tuberculosis [11], autoimmune disease [12], cardiovascular disease [13,14], diabetes mellitus [15], cancer of cervix [16], uterus [17] and breasts [18], and arthritis [19].…”

Section: Introductionmentioning

confidence: 99%

Serum Levels of Glycoproteins are Elevated in Patients with Ovarian Cancer

et al. 2013

View full text Add to dashboard Cite

Identification of reliable biomarkers for detection and staging of cancer and monitoring the outcome of anticancer therapy has been considered to be of high importance. We aimed to estimate the levels of serum glycoproteins, protein bound-hexose, protein bound hexosamine, protein bound fucose, protein bound sialic acid and protein bound carbohydrate in 32 ovarian cancer patients and compared them with the levels that found in 25 normal subjects. As compared to the normal subjects, all the four fractions of glycoproteins level were significantly elevated in ovarian cancer patients (p \ 0.05). Chemotherapy in these patients significantly decreased the levels of serum glycoproteins (p \ 0.05). Thus, high levels of serum glycoproteins in ovarian cancer patients could be due to abnormal protein glycosylation indicating malignant transformation of the cells.

show abstract

“…Likewise, feeding CHO-K1 cells producing EPO with 10 mM ManNAc increased sialylation 136 . Unlike peracetylated ManNAc, ManNAc does not readily cross the cell membrane, and hence rather high concentrations of the latter are required 137 . Consequently, its adoption at large scale is questioned by the inefficient metabolic utilization, but due to the development of acetylated ManNAc analogs, which are metabolized up to 900-fold more efficiently than their natural counterparts 138 , this strategy remains interesting to modulate sialylation.…”

Section: Sialylationmentioning

confidence: 99%

Tailoring recombinant protein quality by rational media design

Brühlmann

Jordan

Hemberger³

et al. 2015

Biotechnology Progress

View full text Add to dashboard Cite

Clinical efficacy and safety of recombinant proteins are closely associated with their structural characteristics. The major quality attributes comprise glycosylation, charge variants (oxidation, deamidation, and C‐ & N‐terminal modifications), aggregates, low‐molecular‐weight species (LMW), and misincorporation of amino acids in the protein backbone. Cell culture media design has a great potential to modulate these quality attributes due to the vital role of medium in mammalian cell culture. The purpose of this review is to provide an overview of the way both classical cell culture medium components and novel supplements affect the quality attributes of recombinant therapeutic proteins expressed in mammalian hosts, allowing rational and high‐throughput optimization of mammalian cell culture media. A selection of specific and/or potent inhibitors and activators of oligosaccharide processing as well as components affecting multiple quality attributes are presented. Extensive research efforts in this field show the feasibility of quality engineering through media design, allowing to significantly modulate the protein function. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:615–629, 2015

show abstract

Increasing the sialylation of therapeutic glycoproteins: The potential of the sialic acid biosynthetic pathway

Cited by 154 publications

References 87 publications

The Emerging Importance of IgG Fab Glycosylation in Immunity

The Emerging Importance of IgG Fab Glycosylation in Immunity

Serum Levels of Glycoproteins are Elevated in Patients with Ovarian Cancer

Tailoring recombinant protein quality by rational media design

Contact Info

Product

Resources

About