Synthesis, conformation, and membrane modifying properties of the trikoningin KB lipopeptaibols: effect of hydrophobicity and chirality in position 1

We synthesized by solution-phase methods the naturally occurring, 10-amino acid residue lipopeptaibol antibiotics trikoningins KBI and KBII, and the [L-Iva(1)] KB analogue, in which the amino acid in position 1 is different, with the aim at investigating the effect of hydrophobicity and chirality in that position. A solution conformational analysis, using FT-IR absorption and CD techniques, indicated that all of the three decapeptides are predominantly helical in a membrane-mimetic environment. Permeability measurements showed an increase of the activity from the [Aib(1)] peptide to the more hydrophobic [Iva(1)] peptides. Conversely, the effect of a change in chirality, obtained by replacing D-Iva(1) with L-Iva, turned out to be of minor significance.