Directed Change in TNFα Specificity to Create DR5 Antagonists
Death receptor 5 (DR5) is a promising target for antitumor therapy due to its high expression on different tumor cells. Resistance of various tumor cells against TRAIL, a natural ligand for the death receptors, reduces its therapeutic potential and prompts the search for novel agonists at these receptors. Previous screening across the combinatorial peptide library yielded a peptide sequence KVVLTHR that specifically binds DR5. Incorporation of this sequence into TNFα resulted in binding DR5 with mutant protein TNFα-mut and appearance of cytotoxicity against lymphoma cells.
Key Wordsdeath receptor 5 TRAIL TNF apoptosis
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- 1.Dai X, Zhang J, Arfuso F, Chinnathambi A, Zayed ME, Alharbi SA, Kumar AP, Ahn KS, Sethi G. Targeting TNF-related apoptosis-inducing ligand (TRAIL) receptor by natural products as a potential therapeutic approach for cancer therapy. Exp. Biol. Med. (Maywood). 2015;240(6):760-773.CrossRefPubMedPubMedCentralGoogle Scholar