Drug Targeting – GalNAc
Targeted drug delivery of therapeutic payloads using N-acetylgalactosamine (GalNAc) conjugates that bind to Ashwell-Morell Receptors (asialoglycoprotein receptors or ASGPR) found in liver hepatocytes has become a leading delivery approach particularly for therapeutic oligonucleotides. We have been active in the field for many years via synthetic development of mono- and multimeric carbohydrate ligands, including GalNAc, for applications including drug targeting.
Vaccine Development – Polysaccharide Chemistry
Bacteria are highly glycosylated pathogens. Glycoconjugate vaccines have been proven to be a successful strategy to prevent infectious diseases with the global pneumococcal vaccine market estimated to be > $8 billion (USD) in 2021. As a CRO, we have been a significant contributor in a variety of glycoconjugate vaccine development projects including preclinical development of a polyvalent (23-serotype) vaccine that may become the world’s most sophisticated broad-range pneumococcal vaccine.
Cancer – Glycans
It is well established that abnormal glycosylation on tumour cells compared to healthy cells is a hallmark of cancer and common to all cancers. Moreover, specific glycans on cell surface proteins actively drive tumour development and progression. New frontiers in drug discovery & development are being realized thanks to discoveries being made in glycobiology. These are paving the way to new therapies centered around cell surface glycans. From development of immune checkpoint inhibitors to treatment vaccines to monoclonal antibodies, glycans will be prominent one way or another. For close to two decades, we have been the leading developer of cancer antigens in the form of oligosaccharides, glycoamino acids, glycopeptides and glycosylated ligands.
Carbohydrate-Protein (Lectin) Interaction
Cell surfaces are decorated with a dense and diverse array of carbohydrate structures (glycans) bound to proteins or lipids anchored in the cell membrane. Collectively, these may be referred to as the glycocalyx. Among a myriad of functions, specific glycan structures engage with complementary carbohydrate recognizing/binding proteins, lectins, to regulate cell physiology. There are many classes of lectins, free circulating or linked to cell surfaces, involved in numerous biological processes. Two of the more actively studied are sialic acid-binding immunoglobulin-type lectins (Siglecs) and the β-galactoside binding lectins (Galectins). Several lectins, including asialoglycoprotein receptors (ASGPR), have been FDA-approved as viable for application to targeted drug delivery systems. Expanding knowledge in this area promises new opportunities for therapeutic intervention. With two decades of experience synthesizing a multitude of glycan systems, we are here to help advance discoveries and therapeutic applications in this field.