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The mechanism of thalidomide side effects has been elucidated in this way!

In 2010, Ito et al. Science group announced that they discovered a protein involved in the side effects of thalidomide. Thalidomide caused severe disability (teratogenicity) in children when taken as a sleeping pill by pregnant women. This is known around the world as a side effect of the drug. But, it had remained a mystery for many years why side effects occur. The group of Ito et al. succeeded in finding cereblon (CRBN), which is the causative protein of the side effects of thalidomide, by a method called phishing (chemical pull-down) using magnetic beads "FG beads". Thalidomide was immobilized on the surface of the FG beads, and the protein to which thalidomide acts (binds) was purified using a magnet from the lysate in which innumerable proteins exist. FG beads are tiny plastic spheres that contain ferrite inside and can be attracted by a magnet. Cereblon is a component of an enzyme called ubiquitin ligase, which is involved in proteolysis, and it has been clarified that when thalidomide binds to cereblon, it caused limb malformations. It is expected that new drugs that suppressed the side effects of thalidomide will be developed by utilizing the findings of this study.

Experimental using chicken eggs

Related papers:
Identification of a Primary Target of Thalidomide Teratogenicity
Reference documents using the FG beads


Applications

FG beads are often used for chemical pulldowns and immunoprecipitation. Chemical pulldowns are performed to identify the target protein of a compound (drug, natural product, toxic substance, etc.) as in the thalidomide experiment described above. By identifying the target protein, the mechanism of action can be elucidated, and it becomes possible to discover disease diagnostic markers and develop new therapeutic agents. Up to now, it has helped target searches for many compounds such as drugs, natural products, and toxic substances, and has contributed extensively to the field of chemical biology. Not only compounds can be immobilized on FG beads, but also antibodies can be immobilized for immunoprecipitation, and proteins, DNA, etc. can also be immobilized, resulting in a wide variety of uses. Recently, it has been widely used for research on antibody drugs and development of diagnostic methods for diseases.

Example of use:
https://fgb.tamagawa-seiki.com/en/technique/identification/index.html

When using FG beads, first select from the lineup according to the functional group of the target ligand(compound (drug), protein, DNA, etc.). After immobilizing the ligand according to the recommended protocol, the next step is affinity purification of the targets.

Protocol:
https://fgb.tamagawa-seiki.com/en/protocol/index.html

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