Investigations of the mode of action of feglymycin on the bacterial cell wall biosynthesis

• Applicant: Professor Dr. Roderich D. Süßmuth
• Subject Area: Biological and Biomimetic Chemistry
• Term: from 2013 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 237444298

The linear 13 mer Peptide feglymycin is composed of non-proteinogenic amino acids 4-hydroxyphenyl glycine and 3,5-dihydroxyphenylglycine. It has a remarkable activity against the HI-virus and a very good antibacterial acitivy against methicillin-resistant Staphylococcus aureus strains (MRSA). After perfroming the total synthesis we identified possible targets of the bacterial cell wall synthesis, the enzymes MurA and MurC. Hence, we synthetically peformed a full Ala-scan of feglymycin. The biological testing of 13 Ala-feglymycins against the enzymes and in vitro resulted in different contributions of amino acids to bioactivity. We intend performing studies on the molecular targets of feglymycin, particularly supported by synthetic labels as photolabels and fluorescence labels. This apporach will be further supported by proteomc approaches. We intend to structures of feglymycin in solutions and bound to protein targets. This work will have a a significant impact on evaluating feglymycin for its potential as a peptide drug.

• DFG Programme: Research Grants