Drug Design and Optimization

This group is located at the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS)

In order to combat the increasing number of resistant pathogens, the development of new antibiotic drugs is an important goal for pharmaceutical research. Lacking in this field are efficient medications that fight infectious diseases. As a result, scientists are constructing and improving novel agents that target essential processes in bacteria. This is done with the aim of killing or attenuating these pathogens. Below, you may read more about the optimization of new drug candidates.


Our Research

Impression of a laboratory of HIPS research group "Drug Design and Optimization"

The department of “Drug Design and Optimization” develops molecules that avoid the increasing resistances of pathogens to commonly used antibiotics. Those new drugs should interfere in essential processes within the bacteria in order to kill them or to switch off their protective mechanisms.

One of those essential processes in bacteria is the transcription of their genetic information. The inhibition of such an important function leads to the bacteria’s death. Therefore, scientists focus on the development of an inhibitor that blocks the transcription of bacterial genes. The new molecule is intended to inhibit the so-called RNA polymerase (RNAP), an enzyme that plays an essential role in the survival of bacteria. This enzyme transcribes DNA into RNA, thereby enabling the cell to produce proteins from the genetic information. The targeted bacteria are those that infect humans and cause serious diseases. One example is Mycobacterium tuberculosis, the cause of tuberculosis and thereby of two million deaths per year worldwide.

Since commonly used antibiotics are ineffective due to increasing resistance, the availability of new drugs becomes more and more urgent. For that reason, scientists develop new inhibitors of the RNAP of bacteria to characterize its mechanism and to optimize it. This approach ensures that the agent is not only highly potent, but that it also entries pathogenic cells where it can unfold its antibiotic effect.

Thermodynamic characterization of drug candidate

Another vitally important mechanism for bacteria is the so-called “quorum sensing” – the bacterial communication among each other. Using chemical signals known as autoinducers, bacteria “talk” with one another. These signal molecules regulate properties as for example virulence factor production or biofilm formation in a cell density-depending manner.

Bacteria build a dense layer, the biofilm, which enables self-protection against an immune response. Additionally, biofilms can suppress the uptake of antibiotics resulting in resistant bacteria. The research group focuses on a signal molecule, termed PQS, which only exists in the human pathogenic bacterium Pseudomonas aeruginosa and promotes the generation of biofilms and the production of virulence factors.

The aim of the scientists is to develop agents that inhibit the synthesis and activity of PQS. An infection with Pseudomonas is considered to be an extreme impairment, especially for patients suffering from cystic fibrosis. Bacteria, which live in the tough mucus lining the lung, eventually form biofilms that frequently lead to life-threatening pneumonia.

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  • HIPS Infofilm (English)

    Resistance to antibiotics has become one of the major global challenges regarding infectious diseases. This is specifically the issue that is being tackled by the new Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS).

Audio Podcast

  • Kündigung für Biofilm-WGs – Pharmazeuten des HIPS stören BakteriengemeinschaftenBakterien haben einen ausgeprägten Gemeinschaftssinn und verschanzen sich gerne in schleimigen Biofilmen. Etwa 60 Prozent aller bakteriellen Infektionen lösen inzwischen Biofilme aus. Ein besonders geselliger Keim ist Pseudomonas aeruginosa. Er ist besonders für Mukoviszidose-Patienten gefährlich. Wissenschaftler am Helmholtz-Institut für Pharmazeutische Forschung Saarland suchen nach Wegen, seine Biofilme aufzulösen – damit Medikamente wirken können. Begleiten Sie Anke Steinbach in Ihre Labore...
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