There is world-wide a growing resistance of bacteria against common antibiotics. To combat such multi-resistant bacteria, new antibiotics are urgently needed. Antimicrobial peptides (AMPs) are one promising class of novel compounds with the potential to overcome bacterial resistance against established antibiotics. In continuation of our work in medicinal inorganic chemistry, we have successfully modified the activity of short AMPs by substitution with metal complexes. Derivatization of short AMPs with metallocenes yielded not only more active derivatives. Also, depending on the nature of the metallocene and its place within the peptide sequence, we could extend the activity of the conjugate to otherwise resistant strains. In collaboration with microbiologists, the mechanism of action of our new metal-containing AMPs was elucidated. Interestingly, additional activity resides with the redox properties of the metal complex, and their drastically reduced hemolytic activity opens the potential for systemic applications. |