Small Molecules Hit It Big new therapeutic approaches against viruses, bacteria, and cancer

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Scientists at the Freie Universität Berlin and the NeuroCure Cluster of Excellence led by biochemist Volker Haucke in collaboration with colleagues from Australia and the Leibniz Institute for Molecular Pharmacology (FMP) in Berlin have developed small molecules that inhibit the internalisation of important signaling molecules, but also of pathogenic organisms such as the immunodeficiency virus (HIV) and bacteria in cells. These substances inhibit the function of the cellular scaffold protein clathrin und can serve as a starting point for new therapeutic approaches for the treatment of cancer, viral or bacterial infections, or neurological disorders. These results were published in the latest edition of the prestigious journal cell.

The inclusion of important signaling molecules such as growth factors but also communication within the nervous system depends on the intracellular scaffold protein clathrin. Clathrin is involved in the production of small only about 100 nm size vesicles (a nanometer is equal to as little as 1/billion metres). These vesicles shuttle signaling molecules in the cell Interior or serve as storage areas for the capitalised version of the transmitter in the nervous system. The scientists used compound libraries small molecule that consists of approximately 20,000 different substances medicinal chemistry-based synthesis was coupled to identify small molecules that specifically bind of clathtrin to his partner proteins brakes. These compounds called pit stops are able to within a few minutes to prevent the recording of the signaling molecules, which stimulate cell growth and Division, or the indication of the human immunodeficiency virus (HIV) in cells. Using shiny fluorescent proteins that could identify the scientists reduced dynamics of clathrin and its partners as the underlying reason for the block internalisation. "Vesicle formation appears to hang as if you had your cells put into the freezer," explains Professor Haucke. Similar effects have been observed in lamprey and cultured nerve cells of mice or rats treated with pit stops resulting in a block in the vesicle Reformation and transmission. Many neurological disorders, such as epilepsy are caused by overexcitability of nerve cells damping of transmission by pit stops and if substances may open up new possibilities for the treatment of these diseases. "Clathrin-mediated uptake in cells is of such fundamental importance that the development of these inhibitors can develop new concepts for the treatment of so far incurable cancers such as brain tumours-tumours whose growth depends on the internalisation of the signaling molecules, which promote cell division, perhaps" explains Volker Haucke NeuroCure scientist.

Sources: Freie Universität Berlin, AlphaGalileo Foundation.