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A computational strategy was used to design helical peptides that can bind to tumor necrosis factor-α (TNFα) dimers to prevent active trimer formation. Three designed peptides showed TNFα inhibition at the cellular level. Chemical crosslinking and mass spectrometry studies verified that these peptides function by breaking TNFα trimers.

Graphical abstract: De novo design of helical peptides to inhibit tumor necrosis factor-α by disrupting its trimer formation

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