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Targeting Protein-Protein Interactions by Small Molecules pp 135–176Cite as

Fragment-Based Drug Discovery for Developing Inhibitors of Protein-Protein Interactions

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Abstract

Protein-protein interactions (PPIs) are important to every cellular process, from signaling pathways to protein post-translational modifications, as well as many cellular machines for complex biological functions. These interactions make up the so-called interactomics of the organism, and aberrant PPIs are the cause of multiple diseases, including aggregation-related Alzheimer’s disease and many types of cancers. Therefore, modulating the protein-protein interactions was considered as the precise way for pharmacological interventions. In this chapter, we first briefly introduced the fragment-based drug discovery and summarized the current consideration for constructing the fragment library and commonly adopted fragment screening methods. In the second part, we first classified the PPIs into four categories based on the interaction pattern and size of interfaces. Then we reviewed recent progress of utilizing the fragment-based drug discovery approach to develop antagonists of various interesting PPIs and organized these case studies into a biological function-oriented way.

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Authors and Affiliations

  1. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China

    Bing Xiong, Qi Wang & Jingkang Shen

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  1. Bing Xiong
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  2. Qi Wang
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  1. School of Pharmacy, Second Military Medical University, Shanghai, China

    Chunquan Sheng

  2. College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA

    Gunda I. Georg

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Xiong, B., Wang, Q., Shen, J. (2018). Fragment-Based Drug Discovery for Developing Inhibitors of Protein-Protein Interactions. In: Sheng, C., Georg, G. (eds) Targeting Protein-Protein Interactions by Small Molecules. Springer, Singapore. https://doi.org/10.1007/978-981-13-0773-7_6

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