Development of Trojan-Horse Conjugates

Antimicrobial drug-conjugates and hybrid antimicrobials


Bacterial resistance has to be understood as an intrinsic part of bacterial evolution. Therefore, novel antimicrobial drugs are continuously needed to counteract bacterial resistance development. Especially, Gram-negative pathogens are difficult to tackle, due to their double-layer cell wall barrier, preventing most antibiotics active against Gram-positive bacteria to enter the Gram-negative cell envelope. However, the efficient permeation barrier of the Gram-negative cell wall has some reardoors, transporters and porins which ensure the the bacteria's supply with nutrition and allows chemical communication to the enviroment. 


In our lab we aim the synthesis of different antimicrobial conjugates, envisaged to enhance drug accumulation and enable translocation across the membrane barrier by utilization of these rear doors. Furthermore, we are interested into antimicrobial hybrids showing dual-targeting features to slow down the occurence of resistance. 


Development of novel cytotoxic payloads for extracellular-targeted drug-conjugates (EDCs)


Extracellular-targeted drug-conjugates of biological sensor molecules with a high affinity for a specific cancer biomarker on cell surfaces and highly potent cytotoxins are an emergent strategy to treat cancer. Due to a higher selectivity compared to conventional chemotherapeutics, these conjuagtes show a significant lower systemic toxicity and bigger therapeutic window.

In our lab we aim the synthesis of novel cytotoxic payloads with new mode of action for the development of extracellular-targeted drug-conjugates (EDCs) for cancer treatment. We focus on a novel strategy to synthesis non-toxic natural product derived prodrugs, which are envisaged to undergo an toxification cascade upon intracellular linker cleavage. We furthermore conjugate appropiate payloads to sensor molecules and biologically evaluate the resulting conjugates together with our collaboration partners.