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)