Chemical Synthesis of TFF3 Reveals Novel Mechanistic Insights and a Gut-Stable Metabolite.

ABSTRACT: TFF3 regulates essential gastro- and neuroprotective functions, but its molecular mode of action remains poorly understood. Synthetic intractability and lack of reliable bioassays and validated receptors are bottlenecks for mechanistic and structure-activity relationship studies. Here, we report the chemical synthesis of TFF3 and its homodimer via native chemical ligation followed by oxidative folding. Correct folding was confirmed by NMR and circular dichroism, and TFF3 and its homodimer were not cytotoxic or hemolytic. TFF3, its homodimer, and the trefoil domain (TFF3_10-50) were susceptible to gastrointestinal degradation, revealing a gut-stable metabolite (TFF3_7-54; t_1/2 > 24 h) that retained its trefoil structure and antiapoptotic bioactiv

SUBMITTER: Braga Emidio N 

PROVIDER: S-EPMC8273887 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature