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-Iva1 KB analo gue, 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 FTIR 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 Aib1 peptide to the more hydrophobic Iva1 peptides. Conversely, the effect of a change in chirality, obtained by replacing D-Iva1 with L-Iva, turned out to be of minor significance.