Discovery of Cyclic Peptide Inhibitors Targeted on TNFα-TNFR1 from Computational Design and Bioactivity Verification.

ABSTRACT: Activating tumor necrosis factor receptor 1 (TNFR1) with tumor necrosis factor alpha (TNFα) is one of the key pathological mechanisms resulting in the exacerbation of rheumatoid arthritis (RA) immune response. Despite various types of drugs being available for the treatment of RA, a series of shortcomings still limits their application. Therefore, developing novel peptide drugs that target TNFα-TNFR1 interaction is expected to expand therapeutic drug options. In this study, the detailed interaction mechanism between TNFα and TNFR1 was elucidated, based on which, a series of linear peptides were initially designed. To overcome its large conformational flexibility, two different head-to-tail cyclization strategies were adopted by adding a proline-glycine (GP) or cysteine-cysteine (CC) to for

SUBMITTER: Zhang J 

PROVIDER: S-EPMC11547827 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature