TCDB is operated by the Saier Lab Bioinformatics Group

1.D.105.  The Channel-forming Polytheonamide (Polytheonamide) Family  

Polytheonamide B (PThB) is a unique peptide natural product with an extremely complex structure, a channel-forming ability in vitro, and an extremely potent cytotoxicity. The 48-mer sequence of PThB consists of alternating d,l-amino acids and possesses an array of sterically bulky beta-tetrasubstituted and hydrogen bond forming residues. These unusual structural features are believed to drive it to fold into a 4.5 nm long tube, form a transmembrane ion channel in plasma membranes, and exert cytotoxicity. Synthetic PThB was utilized for analysis of its cellular behavior. Reflecting its ion-channel function, its addition to cells rapidly diminished the potential across the plasma membrane, and it was also internalized into the cells, accumulating in acidic lysosomes, neutralizing the lysosomal pH gradient. Thus, it is capable of exerting two functions upon causing apoptotic cell death of mammalian cells: It induces free cation transport across the plasma as well as lysosomal membranes.