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Medicinal Chemistry

Marc Nazaré

Profil

Our group is focused on developing new chemical tools to answer fundamental biological questions.

These tools cover a broad range of applications from modulation of protein-ligand and protein-protein interactions, SAR studies, in order to allow for a deeper understanding of signal transduction pathways, molecular recognition phenomena of particular drug targets and other cellular events. Together with our collaboration partners, the medicinal chemistry group optimizes small molecule hits emerging from screening or from rational drug design approaches. These efforts are strongly connected to the activities of the screening unit and the drug design group of the chemical biology platform at the FMP.
Each research project is guided by at least one of the following principles:

  • New chemical structures of the small molecule modulator
  • New unexplored mechanisms of action for a given biological protein target
  • New unexplored biological targets or pharmacological applications/therapeutic concept

As well as applying the principles of classical medicinal chemistry, other state-of-the art methodologies can be utilized and applied as required. These include parallel synthesis techniques, structure based design, compound management, computer modeling and X-ray crystallography.

In this context we are interested in developing and advancing enabling methodologies for the investigation of unexplored biological targets such as library design, synthetic methodology and fluorescent labeling.

Compound management

The FMP screening collection with over 67,000 compounds is managed and continuously extended by the medicinal chemistry group. This compound collection contains sub-libraries including 30,000 drug-like World Drug index derived compounds, 20,000 natural product derived substances, 4,500 fragments, 3,300 FDA approved and experimental drugs with annotated bioactivity and 9,000 compounds donated by more than 35 academic partners worldwide. These efforts ensure a high hit-rate with high quality chemical tools as screening outcome. 

Further information can be found on the FMP Medicinal Chemistry website.

Research

SAR studies and the molecular recognition phenomena underlying protein ligand interactions

We are in particular interested in the role and impact of higher halogens in protein-ligand interactions. Very recently the general relevance of halogen π-interactions in lipophilic protein environments was described as an important and critical protein-ligand interaction which can contribute significantly to the overall affinity. However, in most cases this interaction has been discovered by random variations of substitution patterns and not by a directed rational approach. We intend to rationally exploit this interaction using available structural biology information as well as small, directed halogen biased libraries.

Synthetic methods to access privileged or novel scaffolds useful in drug discovery

The early selection of the appropriate central scaffold for a drug molecule is conceptually a challenging and decisive task in the design of new small molecule modulators. Whereas the peripheral side-chain decoration of a given hit structure is the first and obvious variation starting point, the exchange of the scaffold is inherently more difficult. As well as the underlying complex recognition phenomena, the availability i.e. ease of synthetic accessibility is an important and often underestimated factor for the successful optimization of a lead compound. Therefore we will investigate and develop new synthetic procedures for the synthesis of biologically relevant privileged or novel scaffolds.

News

Marc Nazaré
Marc Nazare
Contact
Phone: +49 30 9406-3083
Max-Delbrück-Centrum für Molekulare Medizin (MDC)
Robert-Rössle-Straße 10
13125 Berlin, Deutschland
Building 87, Room 3.11