Abstract
Herein, we describe the development of a novel staple with an electrophilic warhead to enable the generation of stapled peptide covalent inhibitors of the p53-MDM2 protein-protein interaction (PPI). The peptide developed showed complete and selective covalent binding resulting in potent inhibition of p53-MDM2 PPI.
MeSH terms
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Binding Sites / drug effects
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry*
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Humans
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Lysine / chemistry
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Molecular Dynamics Simulation
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Muramidase / chemistry
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Peptides, Cyclic / chemical synthesis
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Peptides, Cyclic / chemistry*
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Proto-Oncogene Proteins c-mdm2 / antagonists & inhibitors*
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Proto-Oncogene Proteins c-mdm2 / chemistry
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Saccharomyces cerevisiae / chemistry
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Sulfones / chemical synthesis
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Sulfones / chemistry*
Substances
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Enzyme Inhibitors
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Peptides, Cyclic
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Sulfones
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MDM2 protein, human
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Proto-Oncogene Proteins c-mdm2
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Muramidase
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Lysine