In their ongoing quest for new therapies against pathogens, scientists are focusing primarily on chemical and biological agents. These can function as antibiotics or stimulate the immune system. Discovering new drugs, characterising their functionality and optimising their properties are the three main goals of the department “Chemical Biology” at the HZI.
7. Conjugation chemistry
Sugar Conjugates – Exploring the active transport mechanism into gram negative bacteria
Bacteria internalize maltodextrin-based antibiotic through the maltodextrin transporter (Nat Med 2011). Conjugates based on oligomers of maltose are used a transport to deliver the antibiotics into the bacterial cell. This project requires sound skills in sugar chemistry as well as in semisynthesis with natural product-based antibiotics.
Siderophors as targeting moiety
Bacteria satisfy their iron demand through active uptake of self-made and/or foreign siderophor molecules using specific transporters. We try to utilize these transporters for antibiotic uptake by coupling siderophore motifs to antibiotics using a DOTAM/Metal scaffold.
Target Identification of labyrinthopeptins
Labyrinthopeptins are a new class of carbacyclic lantibiotics isolated from Actinomadura namibiensis DSM 6313. These globular structured peptides showed anti-viral and ani-neuropathic pain (in vivo) activities. Our focus is to synthesize probes of these peptides to find out the binding motifs by peptide arrays and by target pulldown approaches.
Secondary target identification through affinity pulldowns with Disorazole A1
Disorazole A1, a metabolite of myxobacterium (Sorangium cellulosam strain So Ce 12) exhibited extraordinarily high antiprofiferative activities (in picomolar ranges) in eukaryotic cells. Mode of action studies based on our profiling methods have suggested that in addition to tubulin, a secondary target may be affected. Our goal in this project is to identify the second target of Disorazole A1 though affinity probes and affinity–based proteomics. The project requires skills in natural product semisynthesis and chemical biology.
8. Natural product synthesis and semisynthesis
Total synthesis of cystobactamids and exploration of structure-activity relationships
Cystobactamids, new natural products isolated from Myxobacteria, showed high biological activity against selected Gram positive bacteria and, most notably, also Gram negative bacteria like E. coli. A modular, multistep total synthesis is developed to provide improved analogs of cystobactamids that should serve as novel antibiotics.
Synthesis of new derivatives of Soraphen A for the exploration of structure-activity relationships
Soraphen A, isolated from the myxobacterium Sorangium cellulosum, is a potent inhibitor of acetyl CoA carboxylase (ACC). Recently, this inhibition has been reported to result in strong immunemodulatory (Nature Medicine 2014) and antiviral (J Hepatology 2015) properties. We have embarked on a synthesis program to improve the in vivo properties of Soraphen A.
Chelocardin: A lead structure to develop broad spectrum antibiotics
Chelocardin is a potent broad spectrum antibiotic produced by Nocardea sulphurea, which has the structural resemblance with Tetracycline. Due to its broad-spectrum antibiotic activity, particularly against ‘ESKAPE’ pathogens, our group is working on improved analogues of chelocardin in order to enhance its bio-activity.
Prof Dr Mark Brönstrup
Head of the department chemical biology
+49 531 6181-3400
Bachelor & Master
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Bachelor, Master and PhD Theses
- Epothilon: Ein HZI-Molekül wird zum Krebsmedikament
- Kleine Moleküle ganz groß – Mit Naturstoffen gegen Hepatitis C
Mit weltweit 130 Millionen Infizierten ist Hepatitis C eine der häufigsten Infektionskrankheiten. Die Therapien, die es derzeit gibt, sind langwierig, haben starke Nebenwirkungen und helfen nicht jedem Patienten. Florenz Sasse vom Braunschweiger Helmholtz-Zentrum für Infektionsforschung und Thomas Pietschmann vom TWINCORE in Hannover suchen gemeinsam nach neuen Wirkstoffen gegen das Hepatitis C-Virus. Hören Sie hier von ihren ersten Treffern und folgen Sie Florenz Sasse zu einer Bibliothek der anderen Art…