A large number of important regulatory pathways in the human body are controlled by protein-protein interactions (PPIs). Inhibition of PPIs would provide possibilities to dissect such pathways and also identify new drug targets1. Since short a-helical structures have been shown to play an important role in several PPIs, they are attractive targets for the design of molecular mimetics2. We are investigating if diketopiperazines (DKPs) with the general structure 1  can be used as a-helix mimetics and disrupt PPIs. Computational studies have revealed that 1  (figure 1) place the interacting substituents (R-groups) in a similar way as residues at the i, i + 4, i+ 7 positions of a a-helix, illustrated as green sphere in figure 1. Figure 1.  General structure 1 and how structure 1 mimic a a-helix. Acknowledgement.   Thanks to the Swedish Research Council for financial support. References (1) Wells, J. A.; McClendon, C. L. Nature.2007 , 7172, 1001.(2) Peczuh, M. W.; Hamilton, A. D. Chemical Reviews.2000 , 7, 2479.

Diketopiperazine-based inhibitors of protein-protein interactions

248th National Meeting (2014)

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