THE AMPHIPATHIC ALPHA-HELIX CONCEPT - APPLICATION TO THE DE-NOVO DESIGN OF IDEALLY AMPHIPATHIC LEU, LYS PEPTIDES WITH HEMOLYTIC-ACTIVITY HIGHER THAN THAT OF MELITTIN

An original serie of 12- to 22-residue-long peptides was developed, th ey are only constituted by apolar Leu and charged Lys residues periodi cally located in the sequence in order to generate ideal highly amphip athic alpha-helices. By circular dichroism, the peptides are proven to be mainly alpha-helical in organic and aqueous solvents and in the pr esence of lipids. The peptides are highly hemolytic, their activity va ries according to the peptide length. The 15-, 20-, and 22-residue-lon g-peptides have LD(50)similar to 5 x 10(-8) M for 10(7) erythrocytes, i.e. they are 5-10 times more active than melittin, and are indeed sev eral orders of magnitude more active than magainin or mastoparan.