Cupiennin 1d*: the cytolytic activity depends on the hydrophobic N-terminus and is modulated by the polar C-terminus.

To investigate structural features modulating the biological activity of cupiennin 1 peptides from the spider Cupiennius salei, three truncated cupiennin 1d analogs were synthesized. The fact that their growth inhibiting effect on Gram-negative and Gram-positive bacteria, their lytic activity with human red blood cells and their insecticidal effect on Drosophila melanogaster correlates with structural properties shows that the hydrophobic N-terminal chain segment includes the major determinants of structure and activity. The polar C-terminus seems to modulate peptide accumulation at negatively charged cell surfaces via electrostatic interactions and has no important effect on the peptides' amphipathic secondary structure.