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.
Metzler-Nolte Group | Ruhr University Bochum, Germany
Nils Metzler-Nolte is Professor of Inorganic Chemistry at Ruhr University Bochum since 2006. His work centers around biomedical applications of transition metal compounds and metal-based drugs. Prof. Metzler-Nolte has received several awards for his work on biological inorganic chemistry, and he was speaker of the DFG-funded Research Unit “Bioorganometallic Chemistry”. He is Associate Editor for Dalton Transactions and member of the Interntional Advisory Boards of several other journals. He has organized several national and international meetings, and is currently Council Member of the Society of Biological Inorganic Chemistry, as well as designated Chair of the Gordon Research Conference Metals in Medicine 2016. Prof. Metzler-Nolte was speaker of the University-wide RUB Research School (funded from the German Excellence Initiative), and served his University as Vice President for Early Career Researchers and International Affairs from 2010 – 2012.
Barbara Hoffknecht is a PhD student in the Metzler-Nolte group, she develops new multi-valent metallocene AMPs.
Marcus Maschke investigates the electrochemical properties of metallocene derivatives as a PhD student in the Metzler-Nolte group, with the aim to understand their anti-bacterial and anti-proliferative activity.
Prof. Julia Bandow is Professor of Microbiology at Ruhr University Bochum, her group investigates the mode of action of novel metal-based antibiotics in close collaboration with the Metzler-Nolte group.
Albada, H. B., Chiriac, A.-I.; Wenzel, M.; Penkova, M.; Bandow, J. E.; Sahl, H.-G.; Metzler-Nolte, N., Modulating the activity of short arginine-tryptophan containing antibacterial peptides with N-terminal metallocenoyl groups, Beilstein J. Org. Chem. 2012, 8, 1753–1764, DOI: 10.3762/bjoc.8.200.
Wenzel, M.; Chiriac, A.-I.; Otto, A.; Zweytick, D.; May C.; Schumacher, C.; Gust, R.; Albada, H. B., Penkova, M.; Krämer, U.; Erdmann, R.; Metzler-Nolte, N.; Straus, S.K.; Bremer. E.; Becher, D.; Brötz-Osterhelt, H.; Sahl, H.-G.; Bandow, J. E., Small cationic antimicrobial peptides delocalize peripheral membrane proteins, Proc. Natl. Acad. Sci. USA, 2014 111, 9225–9234, DOI: 10.1073/pnas.1319900111
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