Glycoproteins and disease
Glycosylation plays a vital role in a multitude of biological processes. It is no surprise that it has become a key area of study to understand human diseases. The importance of the glycome –the complete set of sugar composition of a cell or organism– was first evidenced by studies of rare genetic disorders that affect glycosylation.
Since then, several clinically important glycoproteins have been identified. Their glycosylation patterns are an indication of disease outcome or disease progression. Changes in glycan composition can influence inflammatory responses, viral entry, or cancer cell metastasis.
Many autoimmune diseases involve abnormal glycosylation of one or more glycoproteins. Among these are IgA nephropathy, lupus and inflammatory bowel disease.
Diseases like diabetes trigger abnormal glycan-mediated signalling pathways and upregulate the glycosylation of several proteins.
Changes in glycosylation patterns of specific proteins were one of the first biomarkers of cancer. They are still regularly used as a diagnostic tool and to assess the patient prognosis and response to treatment.
Examples of such glycoproteins include CEA, MUC1, MUC16 and prostate-specific antigen (PSA). Glyco-selective lectins have proven a useful tool for the identification of novel PSA biomarkers.
Infection and the immune response are processes that rely heavily on glycosylation. One clear example is the mechanism of action of HIV.
The HIV envelope spike protein (Env), highly glycosylated, is critical for the viral cell entry and immune evasion mechanism. A better understanding of the glycan structure of Env has been key in contributing to the recent progress in HIV-1 vaccine development.
Another example is the infection by SARS-Cov-2, the virus that causes COVID-19 disease. Research on the glycosylated viral Spike protein has been crucial to understanding the mechanism of infection. But it is not only the viral glycoprotein that plays a role in the outcome of infection.
Recent studies suggest that the absence of alpha-anti-trypsin (ATT) correlates with high transmission of the variant of SARS-CoV-2 bearing a Spike 614G mutation. The human glycoprotein AAT normally protects the lungs and liver from the harmful effect of neutrophil elastases. The 614G mutation introduced an additional neutrophil elastase cleavage site to the Spike. An AAT deficiency, more common among European and North American populations, eases Spike activation, resulting in a faster spread of this mutant.
Therapies and new tools
Glycan profiling of specific proteins, or the whole glycome, has several and important applications in diagnostics and therapies. These applications are especially relevant for cancer, immunological conditions and inflammation.
The efficacy of therapeutic antibodies is also influenced by glycosylation. There is great potential for improvement of these biopharmaceuticals through glyco-engineering.
At GlycoSeLect, we develop tools based on Prokaryotic Recombinant Lectins (RPLs). RPLs are enhanced affinity proteins that enable efficient detection, analysis and isolation of glycosylated molecules.
RPLs are an effective and valuable analytical resource for glycoprotein characterization. They can be used in combination with high-throughput tools like ion mobility spectrometry, providing an efficient and selective way to monitor glycan changes in a bioprocess.
If you are looking to assess the glycosylation of clinically important biomarkers, without the release of glycans, learn more about our RPLs here.
Contact us today to know more about glycoprotein analysis and separation products.