Researchers have developed a method to engineer sugar clusters attached to proteins or lipids, called glycan complexes, to target particular organs of the body. A team from the Riken Biofunctional Synthetic Chemistry Laboratory in Japan and Kazan Federal University in Russia published their work in Advanced Science.
The engineered sugar clusters could lead to glycocluster-based diagnostic tools with improved selectivity and precision compared to peptide or antibody-based tracers, according to the group.
Glycans, chains of sugar molecules found on the surfaces of cells, play important roles in cellular communication and recognition of foreign pathogens. Previous work has shown that glycans can form heterogeneous groups of different sugars, forming patterns that enable them to fit with particular proteins.
The team of researchers examined whether the patterns were random or could purposefully influence the movement of proteins and cells throughout the body. The team selectively attached 2 different glycans to the protein albumin in specific patterns, where the sugars were either ordered randomly or in a specific sequence. They injected the heterogeneous glycoclusters into mice and used noninvasive imaging to track the conjugates movement.
The team compared the heterogeneous clusters with homogeneous clusters that contained 1 type of glycan. Heterogeneous glycoclusters had significantly different properties from the homogeneous groups, such as selectively accumulating in the liver.
“This work shows that the heterogeneity of clusters does indeed play an important role in creating strong and selective binding in vivo. In the same way that burrs–and Velcro, which was developed based on the idea–attach powerfully even though each individual bond is weak, biological molecules often attach together using weak covalent bonds that together form a strong connection,” lead researcher Katsunori Tanaka said in prepared remarks. “In addition, using multiple glycan molecules–or in other words, heterogeneity–allows us to promote selective interactions with target molecules through pattern recognition. Hence, precisely controlling the configuration of the glycans may allow us to design new glyco-conjugates that can be used to target certain tumors, for example.”