Disclosed herein are novel
antimicrobial peptides with useful, improved, or superior properties such as
antimicrobial activity, desirable levels of hemolytic activity, and
therapeutic index against a broad range of microorganisms including
gram-negative and
gram-positive
bacteria and other organisms having a cellular or
structural component of a
lipid bilayer membrane. Also provided are methods of making and using such peptides to control microbial growth and in pharmaceutical compositions for treatment or prevention of infections caused by such microorganisms. Certain peptides are disclosed utilizing a structure-based
rational design relating to an
antimicrobial peptide, V681, with single D- / L-
amino acid substitutions or charged residue substitutions in or near the center of the
peptide on the nonpolar or polar face. Also disclosed are peptides with one or more amino acids in the D configuration, including peptides with all amino acids in the D configuration. Modified
peptide analogs herein can demonstrate one or more properties such as improved antimicrobial activity, specificity, and resistance to degradation. Compositions disclosed herein have useful clinical potential as
antibiotics including
broad spectrum antibiotics.