Have Glycans Finally Found a Place in Medicine?
Complex sugar molecules called glycans are an essential component to life as we know it since they are estimated to be the most abundant class of organic molecules on Earth. They are present in all domains of life, taking different shapes and sizes – from a single monosaccharide to the complex polysaccharides containing thousands of units. Oppose to DNA and proteins, glycans have been rather neglected by the medical field, however, nowadays things are rapidly changing.
At the beginning of 20th century, differential blood types – A, B and O were discovered, enabling the first successful blood transfusion. However, their true chemical identity was revealed only 50 years later and it is based, as you’re probably guessing, on differential glycan structures. The beginning of 20th century was also marked by the discovery of heparin, a polysaccharide which is nowadays routinely used for the treatment of thrombosis. The initial boost of “glycodiscoveries” was somewhat dampened because of pronounced structural complexity of glycans, which could not be resolved by existing techniques. With the development of analytical techniques, our knowledge on glycan structures deepened, leading to significant breakthrough about the important roles that glycans play in our body. For instance, now we know that glycans control the function of our antibodies, which are crucial for our defence against various microorganisms. These findings also enabled the construction of dedicated biologics – monoclonal antibodies with the desired characteristics and controlled effects on the immune response. Moreover, glycans were found to be an integral part of numerous “conventional” drugs from the antibiotic, antimycotic and antiviral class. Some of these drugs also affect glycan-mediated virion assembly, highlighting the prospect for the development of new antiviral therapeutics. Additionally, as viral replicative cycle is usually dependent on the cellular glycosylation, glycan-based strategies can also be used to disrupt this process, which is currently the case for the anti-influenza drugs. Glycans have also hit the spotlight in the vaccine design, where new strategies are being explored, aimed at boosting immunological efficacy against tumour-, bacterial- or viral-associated glycans. Although this approach faces many challenges, it is certainly possible that an anti-glycan immune response will be an important component of future vaccines.
Ever-growing evidence is demonstrating that glycosylation changes in various diseases or that it can act as a trigger to a particular disorder. By understanding the role of these changes, we are given an opportunity for development of new therapeutic approaches and a cognition of novel targets for drug design. So far, the amassed knowledge has enabled the development of antiviral treatments and novel vaccine-design strategies, therefore, glycans will hopefully have their deserved place in medicine.
Glycan-based points of therapeutic intervention (from Valverde et al, Med. Chem. Commun., 2019,10, 1678-1691)
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