Abstract
Native antimicrobial peptides and proteins represent bridges between innate and adaptive immunity in mammals. On the one hand they possess direct bacterial killing properties, partly by disintegrating bacterial membranes, and some also by inhibiting functions of intracellular biopolymers. On the other, native antimicrobial peptides and proteins upregulate the host defense as chemoattractants or by various additional immunostimulatory effects. Structureโactivity relationship studies indicate that residues responsible for the activities on bacterial membranes or for the secondary functions do not perfectly overlap. In reality, in spite of the relatively short size (18โ20 amino acid residues) of some of these molecules, the functional domains can frequently be separated, with the cellโpenetrating fragments located at the Cโtermini and the protein binding domains found upstream. As a cumulative effect, multifunctional and targetโspecific (agonist or antagonist) antimicrobial peptides and proteins interfere with more than one bacterial function at low concentrations, eliminating toxicity concerns of the earlier generations of antibacterial peptides observed in the clinical setting. Copyright ยฉ 2005 European Peptide Society and John Wiley & Sons, Ltd.