Biological therapeutics based on biomolecules have been skyrocketed on the drug market due to their very high specificity, excellent selectivity and resulting high efficiency with resulting reduced side-effects, lower drug attrition and lower development costs. However, there is an urgent need for isotopically-labeled biodrugs utilized for in vitro assays and in vivo (preclinical and clinical) tests.
In contrast with chemical drugs, there is only a very limited number of strategies devised for the specific and selective isotopic labeling of biological molecules because of the size, fragility and complexity of biologicals and also because most of biologics are exclusively soluble in water, a medium which notably disfavors classical chemical reactions.
To date, in most cases, biotherapeutics have been labeled using chemical methods that are only poorly selective and usually give a polydisperse mixture of modified biologics, a situation which makes further analysis of results more complex and prone to biases (figure 1). Therefore, there is a pressing demand from the Pharmaceutical Industry for straightforward, simple, reproducible and chemically benign strategies that enable the isotopically labeling biological molecules in particular with hydrogen and carbon stable isotopes (respectively deuterium and carbon-13), hydrogen and carbon radio-isotopes (respectively tritium and carbon-14) and fluorine-18 (radioisotope for medical imaging).
There is also a lack of specialized chemists capable of devising and implementing such strategies that require an in-depth knowledge of synthetic chemistry and isotopic chemistry but also an intensive experience of biomolecules handling, engineering and analysis. In the same way, there are extremely few mixed Academic/Industrial structures that propose such a training encompassing strategic, scientific and technical aspects of the chemically-benign labeling of biologics.
