Abstract. The H11 antigens, located on the intestinal microvilli of Haemonchus contortus, comprise a group of homologous aminopeptidases essential for the

Molecular conjugation to antibodies has emerged as a growing strategy to combine the mechanistic activities of the attached molecule with the specificity of antibodies. A variety of technologies have been applied for molecular conjugation; however, these approaches face several limitations, including disruption of antibody structure, destabilization of the antibody, and/or heterogeneous conjugation patterns. Collectively, these challenges lead to reduced yield, purity, and function of conjugated antibodies.

Abstract. The H11 antigens, located on the intestinal microvilli of Haemonchus contortus, comprise a group of homologous aminopeptidases essential for the

Therapeutic monoclonal antibodies are central to cancer treatment but often show incomplete efficacy. Cheng et al. demonstrate that transient host-cell glycoengineering to reduce N-glycan trimming strengthens IgG-FcγRIIIa bond resilience under vascular flow forces and potentiates therapeutic antibody efficacy in lymphoma and melanoma models. This study establishes force durability as an optimization parameter for therapeutic antibodies beyond the affinity-centric paradigm.

npj Vaccines - Glycoengineering of the hepatitis C virus E2 glycoprotein improves biochemical properties and enhances immunogenicity

The collaboration will leverage kyron.bio’s glycoengineering platform to optimise a specific antibody candidate selected by Servier.

Human viruses are easy to change with mutation and they depend on host's glycosylation machinery to add sugars to the viral surface to facilitate infection and evade immune response…

Dysregulated sialic acid biosynthesis is characteristic of the onset and progression of human diseases including hormone-sensitive prostate cancer and breast cancer. The sialylated glycoconjugates involved in this process are therefore important targets for identification and functional studies. To date, one of the most common strategies is metabolic glycoengineering, which utilizes N-acetylmannosamine (ManNAc) analogues such as N-azidoacetylmannosamine (ManNAz) to hijack sialic acid biosynthesis and label the sialylated glycoconjugates with “click chemistry (CuAAC)” tags. Yet, current chemical modifications including those CuAAC-based alkyne/azide tags are still big in size, and the resulting steric hindrance perturbs the mannosamine and sialic acid derivatives’ recognition and metabolism by enzymes involved in biosynthetic pathways. As a result, the peracetylated ManNAz has compromised incorporation to sialic acid substrates and manifests cellular growth inhibition and cytotoxicity. Herein, we show that the α-fluorinated peracetylated analogue ManN(F-Ac) displayed a satisfying safety profile in mammalian cell lines at concentrations as high as 500 μM. More importantly, aliphatic selenol-containing probes can efficiently displace α-fluorine in fluoroacetamide-containing substrates including ManN(F-Ac) at a neutral pH range (∼7.2). The combined use of peracetylated ManN(F-Ac) and the dethiobiotin-selenol probe as the fluorine-selenol displacement reaction (FSeDR) toolkit allowed for successful metabolic labeling of sialoglycoproteins in multiple prostate and cancer cell lines, including PC-3 and MDA-MB-231. More sialoglycoproteins in these cell lines were demonstrated to be labeled by FSeDR compared with the traditional CuAAC approach. Lastly, with FSeDR-mediated metabolic labeling, we were able to probe the cellular expression level and spatial distribution of sialylated glycoconjugates during the progression of these hormone-sensitive cancer cells. Taken together, the promising results suggest the potential of the FSeDR strategy to efficiently and systematically identify and study sialic acid substrates and potentially empower metabolic engineering on a diverse set of glycosylated proteins that are vital for human diseases.

Characterization and Engineering of Drosophila melanogaster β1-3-Galactosyltransferase for Glycoengineering Applications

PI: Edward S.X. Moh (ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia) Keywords: Glycoengineering, Glycosylation, Mass spectrometry, Glycomics, Immobilised enzyme reactors, glycosyltransferases Controlling protein glycosylation as a critical quality attribute of biopharmaceuticals remains challenging when glycosylation is coupled to cellular production systems. Here, we present a proof-of-co...

Read the full paper: Pharmacologic glycoengineering of Fcγ receptor IIIa enhances force-resistant IgG-FcγR interactions and anti-tumor antibody efficacy