1.D.33 The Channel-forming Polytheonamide B (Polytheonamide B) Family
Polytheonamide B, from the marine sponge, Theonella swinhoei, may form a β-helix that is stable in membranes (Oiki et al. 1997; Hamada et al. 2005). It forms channels with cation selectivity: H > Cs > Rb > K > Na (Oiki et al. 1997). Voltage-dependent transitions between brief openings and long closures were observed (Iwamoto et al. 2010; Matsuoka et al. 2011). It has been totally synthesized, and structural permutations have been designed (Ducho 2010; Inoue et al. 2010; Inoue 2011). Derivatives have been characterized with respect to their channel activities (Itoh et al. 2012; Shinohara et al. 2012).
Polytheonamide B (pTB), a highly cytotoxic polypeptide, is one of the most unusual nonribosomal peptides of sponge origin. pTB is a linear 48-residue peptide with alternating D- and L-amino acids and contains a total of eight types of nonproteinogenic amino acids. Hamada et al. (2010) determined the three-dimensional structure of pTB by NMR spectroscopy, structure calculation, and energy minimization. pTB adopts a single right-handed β(6.3)-helical structure in a 1:1 mixture of methanol/chloroform with a length of approximately 45 A and a hydrophilic pore of ca. 4 A inner diameter. These features indicate that pTB molecules form transmembrane channels that permeate monovalent cations as gramicidin A channels do. The strong cytotoxicity of pTB can be ascribed to its ability to form single molecule channels through biological membranes.