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NMR as a Tool to Target Protein–Protein Interactions

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Disruption of Protein-Protein Interfaces

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Abstract

NMR spectroscopy plays a dual role in projects aimed at targeting protein–protein interactions (PPIs).While it has been extensively validated as an efficient technique for the initial screening and identification of weakly interacting fragments and for subsequently guiding their optimization into molecules with higher affinity and more favorable drug-like properties, it also represents an extremely powerful tool to monitor the formation of protein–protein complexes in solution and to obtain structural information on these adducts. It allows the identification of the protein interfaces and, in some cases, provides intermolecular distance and orientational restraints that lead to the definition of the relative arrangement of the two proteins. In particular, it constitutes the structural technique of choice for studying weak/ transient protein–protein interactions, which represent the natural targets for drug discovery projects addressing PPIs.

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  1. Magnetic Resonance Center (CERM), University of Florence, Via Luigi Sacconi 6, 50019, Florence, Sesto Fiorentino, Italy

    Rebecca Del Conte, Daniela Lalli & Paola Turano

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  1. Rebecca Del Conte
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  2. Daniela Lalli
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  1. , Department of Biotechnology, Chemistry a, University of Siena, Siena, Siena, I-53100, Italy

    Stefano Mangani

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Del Conte, R., Lalli, D., Turano, P. (2013). NMR as a Tool to Target Protein–Protein Interactions. In: Mangani, S. (eds) Disruption of Protein-Protein Interfaces. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-37999-4_4

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