Abstract
Membrane-active natural and synthetic peptides and peptidomimetics are becoming
the focus of interest because they might represent a promising approach to overcome increasing antibiotic resistance. In parallel, since the late 1960s less research has been performed to find new antibacterial drugs and today, in 550
drugs currently under development, only six are new antibiotics.
Pathogens can acquire resistance by various mechanisms that are based
on modifications of the receptors specific for the drugs. However, there is one class of antibiotics that does destroy the membrane integrity without necessarily needing a specific protein or DNA receptor: antimicrobial peptides (AMPs)
or membrane-active molecules that interact with the lipid bilayer of the cells. They change the biophysical properties of the bilayer, can dissolve lipids in a detergentlike manner or form transmembrane pores. In all cases cell lysis is eventually observed and the bacteria killed. These are the most interesting antibiotics because
in can be expected that resistance against these molecules is not or hardly being developed. Several hundred membrane-active AMPs (A. Tossi, http://www.bbcm.univ.
trieste.it/) have been discovered over recent decades in plants, insects and mammals. In addition, many non-natural membrane-active molecules have been designed for various application.
