At the centre of the method is a new DNA-encoded chemical library (DECL) that contains 35 million different drug candidates. While such collections are nothing new, the structure and scope of the substances contained in this one are something special, the Swiss Federal Institute of Technology in Zurich (ETH) reported in a press release.
Each of the drug candidates contained in the collection consists of a ring-shaped basic structure, to which three different small molecules are attached. “Together, they form a kind of highly-specific fish hook that can bind onto a protein if its form perfectly matches the protein’s structure,” explains ETH researcher Jörg Scheuermann. Short DNA sequences worked like a barcode for the scientists, who used them to identify each fish hook individually. The researchers conducted an experiment in a reaction vessel, observing whether target proteins would be caught on one of the 35 million fish hooks. In this way, they were able to very quickly test the whole collection for potential matches in one go.
DECL technology has caught on in the pharmaceutical industry in recent years. According to Jörg Scheuermann, the ETH researchers are coming closer to antigen-antibody interactions by using molecules that possess three or more chemical hooks. His team also outlined a new treatment approach, which involves linking a cytotoxin to a specific protein binder. This would then use the protein to recognise a tumour cell, attach to it and release the toxin in a high local concentration, which would cause the death of the tumour cell. Previously, this strategy has been implemented with antibodies, but they are relatively large and therefore not able to penetrate tumour tissue well.
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