Department of Chemistry, New York University, 100 Washington Square East, New York, New York 10003, USA.
We report an application of the principle of multivalency to create new antimicrobial agents using the reactive polymaleic anhydride (PMA) chain to link antimicrobial tetrapeptides to afford multivalent variants containing approximately 40 monomer units. Relative to the free peptides, the product shows a 10-fold improvement in IC(50) without provoking more severe hemolysis of red blood cells. Thus, multivalency or polyvalency may offer a route to enhance the activity of antimicrobial peptides.