Class II Lanthipeptides
Class III Lanthipeptides



Coworkers: Dr. Agnes Mühlenweg, Melanie Gonsior

Keywords: amino acid and peptide synthesis, structure-activity-relationship studies, anti-HIV-1 activity

Cooperation: Prof. Dominique Schols, Katholieke Universiteit Leuven, Belgium, Prof. Hans-Georg Sahl, Universität Bonn, Prof. Ulrich Koert, Universität Marburg, Prof. Anne Ulrich, Universität Karlsruhe

Fig.1 Primary structure of Feglymycin

The 13-mer peptide Feglymycin (figure 1) was isolated from Streptomyces sp. in the mid 1990's by Hoechst company (now Sanofi, Frankfurt, Germany) and exhibits remarkable antiretroviral and antibacterial activity. It's X-ray crystal structure shows a double-stranded antiparallel-helical dimer stabilized by a network of intermolecular hydrogen bonds (figure 2). We developed a convergent and stereoselective total synthesis for Feglymycin by condensation of repeating peptide fragments, which enables fast access to new derivatives (figure 3). Interestingly, Feglymycin exibits remarkable activity against various resistant HIV-1 strains and it also inhibits syncytia formation which often occurs in a late stage of an HIV infection. The target for the antibacterial (MIC = 2.0 µg/ml) as well as the antiviral activity (IC50 = 1.9 µg/ml)[ of Feglymycin is not known yet. In order to obtain a more detailed view on the mode of action of this naturally occurring peptide further structure-activity relationship studies are planned.