Characterization of unique amphipathic antimicrobial peptides from venom of the scorpion Pandinus imperator

Two novel antimicrobial peptides have been identified and characterized fro m venom of the African scorpion Pandinus imperator. The peptides, designate d pandinin 1 and 2, are alpha -helical polycationic peptides, with pandinin 1 belonging to the group of antibacterial peptides previously described fr om scorpions, frogs and insects. and pandinin 2 to the group of short magai nin-type helical peptides from frogs. Both peptides demonstrated high antim icrobial activity against a range of Grampositive bacteria (2.4-5.2 muM). b ut were less active against Gram-negative bacteria (2.4-38.2 muM), and only pandinin 2 affected the yeast Candida albicans, Pandinin 2 also demonstrat ed strong haemolytic activity (11.1-44.5 muM) against sheep erythrocytes, i n contrast with pandinin 1, which was not haemolytic. CD studies and a high -resolution structure of pandinin 2 determined by NMR, showed that the two peptides are both essentially helical, but differ in their overall structur e. Pandinin 2 is composed of a single alpha -helix with a predominantly hyd rophobic N-terminal sequence. whereas pandinin 1 consists of two distinct a -helices separated by a coil region of higher flexibility, This is the firs t report of magainin-type polycationic antimicrobial peptides in scorpion v enom. Their presence brings new insights into the mode of action of scorpio n venom and also opens new avenues for the discovery of novel antibiotic mo lecules from arthropod venoms.