Medicinal Chemistry (Marc Nazaré)

Research Interests [ • ]          Compound Management [   ]

Research interests

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. 

This work embraces the following further areas/fields of interest:

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. 

Leibniz-Forschungsinstitut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V. (FMP)
Campus Berlin-Buch
Robert-Roessle-Str. 10
13125 Berlin, Germany
+4930 94793 - 100 
+4930 94793 - 109 (Fax)

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