Tumor Necrosis Factor-α Trimer Disassembly and Inactivation via Peptide-Small Molecule Synergy.

ABSTRACT: Aberrant signaling by tumor necrosis factor-α (TNFα) is associated with inflammatory diseases that can be treated with engineered proteins that inhibit binding of this cytokine to cell-surface receptors. Despite these clinical successes, there is considerable interest in the development of smaller antagonists of TNFα-receptor interactions. We describe a new 29-residue α/β-peptide, a molecule that contains three β-amino acid residues and three α-aminoisobutryic acid (Aib) residues, that displays potent inhibition of TNFα binding to TNFα receptor 1 (TNFR1) and rescues cells from TNFα-induced death. The complement of nonproteinogenic residues renders this α/β-peptide highly resistant to proteolysis, relative to all-α analogues. The mechanism of inhibitory action of the new 29-mer involves dis

SUBMITTER: Checco JW 

PROVIDER: S-EPMC7654703 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature