Abstract
A highly cytotoxic extract from marine sponge, polytheonamide B, is a linear 48-residue peptide. Alternative D-and L-forms of unusual amino acids suggest formation of β-helix that is stable in membrane and serves for ion conducting pore. The NMR study indicated that polytheonamide B forms β-helix in methanol/chloroform solution. Channel activity of polytheonamide B was examined using planar lipid bilayers. Ionic current appeared from pM concentration. Measurements of the reversal potentials revealed that the channel showed cation selectivity. Single channel current was recorded in symmetrical 1 M solutions. The selectivity sequence was: H+>Cs+>Rb+>K+>Na+. Single-channel I-V curve exhibited slight inward rectification. Voltage-dependent transitions between brief openings and long closures were observed. Orientation of the peptide in the membrane was fixed when the peptide was added to one side of the chamber. The asymmetric behaviors, such as single channel rectification, voltage-dependent gating and oriented incorporation into the membrane, must be correlated to the molecular structure of polytheonamide B.
