Sugar-Coated Catalysts That Work In Live Mice

Carbohydrate structures called glycans could help researchers send metal catalysts to specific tissues without the need for time-consuming antibody development.

AsianScientist (Feb. 27, 2017) – Researchers from Japan have developed a catalyst that can be delivered to specific sites in the body without the use of antibodies. Their results, published in Angewandte Chemie, could make organometallic catalysis applicable for therapy or diagnostics.

In recent years, non-invasive targeting for therapy, biological sensing and imaging has become one of the most active biomedical research areas. The ability to precisely control the location of a catalyst in the body could be used to synthesize bioactive molecules and drugs exactly where they are needed, thereby reducing the amount of drug required and lowering the risk of side effects. However, targeting catalysts to tissues has only been achieved in bacteria or in vitro so far.

Now, a team of researchers led by Katsunori Tanaka and his colleagues at RIKEN, Waseda University and the Japan Science and Technology Agency (JST) have developed a gold catalyst that can be delivered to target organs in mice where it performs a chemical transformation visualized by bioimaging.

Gold catalysts are biocompatible and could potentially be used to perform synthetic transformations in target tissues. The challenge, however, is to bring the gold specifically to its target organ and to establish a visualization scheme to monitor the ongoing biochemical transformation.

To get around this problem, the researchers used albumin, an abundant water-soluble protein. Firstly, they used gold ions conjugated to a hydrophobic protein ligand which can be bound to albumin. The albumin is then furnished with sugar-type molecules called glycans, which carry the chemical groups to the target organs.

In this way the glycoalbumin complex can deliver the biocompatible gold catalyst to the target tissue. Intriguingly, the gold complex acts as an efficient organometallic catalyst that can perform the reaction between biologically relevant molecules and organic substrates, which means it could be a relevant drug or diagnostic compound.

The scientists used the gold complex to bind a fluorescent dye to certain surface proteins present in the target tissue, which was either the liver or the intestine. To visualize the reaction, they performed fluorescent imaging of the whole living mouse.

Within two hours after the injection of the catalyst and the substrate (the functionalized fluorescent dye) into the blood circuit, strong fluorescence in the two organs demonstrated successful in vivo gold catalysis. Thus, a catalytically active gold complex was sent and delivered to a target organ within a short time and without the laborious development of antibodies.

As an outlook the scientists envisage biomedical applications, especially for metal catalysts with their unique reactivities:

“Example therapies may include uncaging of active, cancer therapeutic enzymes selectively at tumor sites or […] reactions to produce active drug molecules at targeted organs,” they wrote.

The article can be found at: Tsubokura et al. (2017) In Vivo Gold Complex Catalysis within Live Mice.


Source: Wiley; Photo: Shutterstock.
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