Peptides & Proteins

More than 50% of human proteins are glycoproteins, which tend to be heterogeneously glycosylated. That means the structures of attached sugars and the sites to which they're attached are variable. Glycosylated natural products like the macrolide antibiotics and anthracycline antitumor agents also can exhibit some variation in their glycosylation pattern. Whether glycoproteins and glycosylated natural products are heterogeneously glycosylated or not, there is a strong need to better control which sugars go where on these molecules, because sugars are often essential to the functions of biomolecules. Thus, the ability to modify and control which ones are attached and exactly how they're attached can make it possible to tailor biomolecular structure, folding, stability, immunogenicity, uptake, distribution, target recognition, and other properties and functions of these compounds.

For example, glycosylated biomolecules can be turned into better drugs by manipulating their sugars. Appropriate glycosylation of erythropoietin (EPO), an approved glycoprotein drug for anemia and cancer, is critical for its activity and longevity of action, and its properties have been improved by modifying its glycosylation through genetic engineering. It would be beneficial to the development of therapeutic proteins to be able to totally control the glycosylation of drugs like EPO. For instance, introduction of modified N-glycans into EPO have increased the its activity and prolonged the duration of action, thereby reducing the frequency with which EPO must be administered. Elimination of fucose from monoclonal antibodies can increase the interaction of these proteins with their cell receptor antigens 50-fold. But EPO and most other glycoprotein drugs are currently produced commercially in mammalian cells, which express them as mixtures of different glycoforms (versions with variable glycosylation), and this is a hard process to control. Solutions to this problem are being sought through engineering new methods for protein glycosylation in bacteria, yeast and plants.

Because glycosylation of proteins plays an important regulatory role in protein function, especially in eukaryotic organisms like humans, there is a great need to develop chemical methods for peptide and protein glycosylation. CarboConnect can easily be applied to the synthesis of sugar targeted variants or specific glycopeptides and glycoproteins.