Projects

Translocation Transfer

Mark Brönstrup

Affiliation:

Helmholtz Centre for Infection Research
Inhoffenstr. 7
D-38124 Braunschweig
Germany

Contact:

Phone +49 531 6181 3400
Email: mark.broenstrup@helmholtz-hzi.de
Website: www.helmholtz-hzi.de/broenstrup

Current Position:

Head of Department of Chemical Biology (CBIO), Professor (W3) at the Leibniz University of Hannover

Keywords:

Antiinfective drug discovery, natural products, mass spectrometry, metabolomics

Research profile:

Discovering new antibacterial and antiviral drugs, characterizing their functionality and optimizing their properties are the three main goals of the department “Chemical Biology”. An assay development and medium throughput screening unit is used to find starting points for small molecule antiinfectives. Their mode of action is elucidated by targeted and untargeted mass spectrometry-based metabolomics, peptide arrays and other techniques.5,6 Hit and lead structures are optimized by a synthetic chemistry group. A special interest concerns the discovery of novel antibiotics against gram-negative pathogens and the design of drug conjugates that effectively overcome their outer membrane. We have developed generic, medium throughput, mass spectrometry-based assays to quantify intracellular drug concentrations in three compartments of gram-negative bacteria, and apply them to profile internal compounds and leads of our IMI Enable/IMI Translocation partners. Translocation of drug conjugates could also be tracked by FAP-based imaging and growth recovery assays.

References:

  • Subcellular Quantification of Uptake in Gram-Negative Bacteria.Prochnow, Hans; Fetz, Verena; Hotop, Sven-Kevin; Garcia-Rivera, Mariel A.; Heumann, Axel; Broenstrup, Mark.Analytical Chemistry (2019), 91 (3), 1863–1872.
  • Multivalent Siderophore DOTAM Conjugates as Theranostics for Imaging and Treatment of Bacterial Infections. Ferreira, Kevin; Hu, Hai-Yu; Fetz, Verena; Prochnow, Hans; Rais, Bushra; Mueller, Peter P.; Broenstrup, Mark Angewandte Chemie Int. Ed. (2017), 56, 8272-8276.
  • In Vitro Model of the Gram-Negative Bacterial Cell Envelope for Investigation of Anti-Infective Permeation Kinetics. Graef, Florian; Richter, Robert; Fetz, Verena; Murgia, Xabier; De Rossi, Chiara; Schneider-Daum, Nicole; Allegretta, Giuseppe; Elgaher, Walid; Haupenthal, Joerg; Empting, Martin; Beckmann, Felix; Broenstrup, Mark; Hartmann, Rolf; Gordon, Sarah; Lehr, Claus-Michael. ACS Infectious Diseases (2018), 4(8), 1188-1196.