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1.D.24 The Marine Sponge Polytheonamide B (pTB) Family 

A cytotoxic peptide, polytheonamide B (pTB), from a symbiotic bacterium in the marine sponge, Theonella swinhoei, has been examined for the cytotoxic spectrum and specific activity to mammalian cells (Iwamoto et al., 2010). pTB is composed of alternative D- and L-amino acid residues throughout the 48-mer peptide. This suggests the formation of a β-helix similar to gramicidin channels. Planar bilayer experiments revealed that pTB forms monovalent cation-selective channels, being compatible with the inner pore diameter of 4Å for a β-helical structure. pTB penetrated vectorially into the membrane, formed a channel by means of a single molecule, and remained in the membrane. These functional properties may account for specific cytotoxic activity (Iwamoto et al., 2010). Functional analysis of synthetic substructures of polytheonamide B have been reported (Matsuoka et al., 2011). 

pTB has more than half of its residues posttranslationally modified. Epimerization reactions result in alternating L- and D-amino acids that allow the peptide to adopt a helical conformation. Other posttranslational modifications include side chain hydroxylations and C- and N-methylations. N-methylations appear to be crucial for stability in a polar environment. They are the driving force for the formation of stable side chain hydrogen-bond chains that act as an 'exoskeleton' (Renevey and Riniker 2016).

The generalized reaction catalyzed by pTB is: 

Monovalent cation (in) ⇌ Monovalent cation (out)

References associated with 1.D.24 family:

Iwamoto, M., H. Shimizu, I. Muramatsu, and S. Oiki. (2010). A cytotoxic peptide from a marine sponge exhibits ion channel activity through vectorial-insertion into the membrane. FEBS Lett. 584: 3995-3999. 20699099
Matsuoka, S., N. Shinohara, T. Takahashi, M. Iida, and M. Inoue. (2011). Functional analysis of synthetic substructures of polytheonamide B: a transmembrane channel-forming peptide. Angew Chem Int Ed Engl 50: 4879-4883. 21520376
Renevey, A. and S. Riniker. (2016). The importance of N-methylations for the stability of the [Formula: see text]-helical conformation of polytheonamide B. Eur Biophys. J. [Epub: Ahead of Print] 27744521