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Total Synthesis of Thielocin B1 as a Protein-Protein Interaction Inhibitor of PAC3 Homodimer

Part of the book series: Springer Theses ((Springer Theses))

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Abstract

Protein–protein interactions (PPIs) play a vital role in numerous cellular functions, and have consequently been identified as novel drug discovery targets. However, it is quite difficult to find suitable drug-like lead compounds that behave as PPI inhibitors because small-molecule inhibitors cannot cover the large interfaces involved in PPIs. The high-throughput screening of a natural products library was conducted to identify potential PPI inhibitors and thielocin B1 was found to be a potent inhibitor of the formation of PAC3 homodimer. Preliminary in silico studies indicated that thielocin B1 was binding to a large hill-like structure on the surface of PAC3. Subsequent analysis of the structure-activity relationships of thielocin B1 and its derivatives showed that thielocin B1 occupied a unique area of chemical space on the surface of the protein, which would otherwise be difficult to reach with traditional synthetic compounds.

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Authors and Affiliations

  1. Max-Planck Institute of Molecular Physiology, Dortmund, Germany

    Kosuke Ohsawa

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  1. Kosuke Ohsawa
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Correspondence to Kosuke Ohsawa .

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Ohsawa, K. (2015). Introduction. In: Total Synthesis of Thielocin B1 as a Protein-Protein Interaction Inhibitor of PAC3 Homodimer. Springer Theses. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55447-9_1

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