The Structure-Function Relationship of Mastoparan : Loss of the Hemolytic Activity of Mastoparan by Substituting Lysine with Ornithine Residues in the Molecule

Abstract

Mastoparan (INLKAIAALAKKIL-NH_2) has a wide variety of cellular effects. To understand the action mechanism of MP, various derivatives with substitutions at the three Lys residues at the 4th, 11th and 12th positions, the Leu residue and the amide structure at the 14th position were synthesized and evaluated in terms of their structure-activity relation ship. The present study showed that Leu^<14>-NH_2 was essential and three Lys residues in MP affected both the hemolytic activity toward bovine erythrocytes and the catecholamine releas ing activity toward bovine adrenal chromaffin cells. The chemical structure of Lys residue rather than the basicity of side chain might be relevant in both activities. The newly designed analog, [Orn^<4,11,12>]-MP had a very weak hemolytic activity towards bovine erythrocytes, but showed a strong catecholamine releasing activity. It is potent and significant, and anticipated to become a more useful tool in the future due to the effective separation between the lytic and catecholamine releasing activities.