Research group

Marc Nazaré

Medicinal Chemistry

Portrait

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 interactions to visualization of proteins by imaging methodologies.

Profile

Design and synthesis of chemical probes for the pharmacological investigation of biological systems
Small molecules can be used as chemical probes to investigate protein function, to elucidate molecular mechanisms and to influence signal transduction pathways. They can also be employed to validate hypotheses from genetic studies such as knock-down- and loss-of-function approaches. Moreover, these substances can serve as starting points for new therapeutic approaches and new drugs.
Goal of our research are the discovery and development of such highly active and selective chemical probes for the specific modulation of protein-ligand or protein-protein interactions. Taking advantage on these optimized tools, in a further step, we also aim at the tailored development of fluorescently labeled probes as well as enzyme-responsive sensors in chemical biology and biomarker applications.

 

Research Interests

Our group is focused on the development of new chemical probes to answer fundamental biological questions. These tools cover a broad range of applications from the direct modulation of protein-ligand and protein-protein interactions to structure-activity relationship (SAR) studies, fluorescent labeling, and targeted protein degradation to allow for a deeper understanding of signal transduction pathways and other cellular events. Together with our collaboration partners, we optimize small molecule hits emerging from screening or from rational drug design approaches. Each research project is guided by at least one of the following principles:

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

Chemical Probes by SAR studies and understanding the molecular recognition phenomena underlying protein ligand interactions

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

The medicinal chemistry group is a chemistry partner site of the European chemical biology infrastructure EU-OPENSCREEN (https://www.eu-openscreen.eu).

Tailoring chemical probes towards imaging sensors for chemical biology approaches

Our SAR studies and the understanding of the underlying protein-ligand interactions allow for the further tailoring of the chemical probes by introducing reporter labels without perturbing the compounds’ affinity and selectivity. This has proven to be a highly effective approach for investigating and validating the physiological role of specific protein targets in proof-of-concept studies. These include unravelling target expression and localization, signaling mechanisms in different cell types, tissues, and in disease state-dependent contexts, in particular by imaging methods. Such labeled small-molecule probes are, for example, capable of visualizing intracellular protein targets in real time and across species, a task which cannot be achieved with traditional antibodies without complex adaptions.

The overarching aim of our research is the development of chemical probes and the advancement of methodologies for the investigation of unexplored biological targets such as SAR studies, library design, synthetic methodology, fluorescent labeling, ligand-directed proximity labeling, targeted protein degradation and enzyme responsive sensors for tailoring our chemical probes for chemical biology approaches. Applications include all research phases, and reach from simple isolated proteins, over cells and tissues to complex in-vivo systems across different species leveraging the inherent translational capabilities of small molecule probes.

Contact

Dr. Marc Nazaré

Head, Nazaré Group

Contact Office

Dajana Baudach

Secretary, Sun Group,
Secretary Nazaré Group


Research Section

Chemical Biology

Members

 People

By PositionA-Z
  • Marc Nazare studied chemistry at the University of Karlsruhe and obtained his PhD in organic chemistry with Herbert Waldmann in the field of natural product total synthesis in 1999. He then joined pharmaceutical industry at Sanofi in Frankfurt as a medicinal chemist. In 2013, Dr. Nazaré started a medicinal chemistry group at the Leibniz Research Institute for Molecular Pharmacology FMP. His current research interests are focused on the design and optimization of chemical probes and imaging tools for chemical biology and translational applications.

  • Dr. Anahid Omran obtained her Bachelor and Master Degrees in Chemistry with a focus on organic synthesis. Afterwards she proceeded to strive into the field of medicinal chemistry to obtain a second Master’s degree from the Southern Illinois University Edwardsville. Focusing her research on the investigation of GPCRs, she received her doctorate from the Friedrich-Alexander University Erlangen, Germany in the group of Prof. Peter Gmeiner. She is currently developing chemical probes for the elucidation of GPCR functions at the Leibniz Research Institute for Molecular Pharmacology as a postdoctoral researcher under supervision of Dr. Marc Nazaré.   

  • Davide got his MSc degree in pharmaceutical chemistry and technology at the university of Milan where he also received his pharmacy certificate. He did his master thesis project in a collaboration between the De Amici`s group at the University of Milan and the Holzgrabe’s group at the university of Würzburg focusing on the development of hybrid ligands for the M1 muscarinic receptor. His PhD at the University of Bergen in the Bjørsvik`s group was funded by the European Commision under the H2020 – MSCA – ITN – 2015 programme (PET3D). As a part of this project, he had also the chance of an industrial secondment at AstraZeneca. During these three years, he mainly focused on the development of XCT inhbitors for cancer treatment and on method development for the functionalisation of imidazoles. In 2020, he joined Dr. Marc Nazaré’s group at the FMP and he is working mainly on the development of selective inhibitors for understudied kinases of biomedicial interest.

  • Annaleah studied chemistry at the Albert-Ludwigs-University in Freiburg, where she completed her bachelor thesis in the group of Prof. Dr Ingo Krossing. For her Master's she moved to Freie Universität Berlin, where she received her Master's degree in Chemistry in 2022 (Master's thesis under Prof. Dr Martin Oestreich) after external research stays at Uppsala University and FMP Berlin. After a three-month industrial internship at Bayer AG, where she was able to further deepen her knowledge in medicinal chemistry - especially regarding PROTACs - she joined our research group in June 2023. Her research focus is on the design and synthesis of smart turn-on fluorescent probes, with the aim to contribute to progress in healthcare through novel diagnostics.

  • Michael studied chemistry at the Freie Universität Berlin, where he received his master's degree in 2022 after research stays at the FMP Berlin, the Ruhr-Universität Bochum and the ETH Zurich. For his master's thesis, as part of the research group of Prof. Dr Beate Koksch, he worked on the stereoselective synthesis of fluorinated amino acids. After a three-month industrial internship at Bayer AG, where he could further deepen his knowledge in the research fields of radiopharmaceuticals and medicinal chemistry, he joined our working group in June 2023. Here, he is working on targeted-activatable luminescence probes for the detection of bacterial infections. Outside of the lab, Michael enjoys sports and is always up for an Apéro.

  • Ziqiong studied Pharmaceutical Engineering at Yunnan University where she got her Bachelor’s. She finished her master thesis in Shanghai Institute of Materia Medica (SIMM), University of Chinese Academy of Sciences where she mainly focused on the design of novel neuroactive steroids. Then she worked as a research assistant in SIMM and did research about transition metal catalysis. She joined the Medicinal Chemistry group at FMP in 2022 as a PhD student to investigate novel inhibitors.

  • Victoria studied chemistry at the University of Vienna for her bachelor’s degree, before pursuing a Master’s degree in Drug Discovery and Development. Her master thesis was written at Boehringer Ingelheim in the Medicinal Chemistry department, focusing on developing an enantioselective way to build up spiro-oxindoles. After her studies, she worked as an analytical chemist in a COVID lab, before moving to Basel for a year and taking part in the Roche internship in Medicinal Chemistry (RiCH) program. Victoria joined the research group of Dr. Marc Nazaré at the Leibniz Research Institute for Molecular Pharmacology in October 2022.

  • Marta studied pharmaceutical chemistry and technology at the university of Milano where she also received her pharmacy certificate. She did her master thesis at the group of Ulrike Holzgrabe at the university of Würzburg where she focused on the design of muscarinic allosteric modulators. She joined the medicinal chemistry group at the FMP in the beginning of 2022 as a PhD student to investigate novel inhibitor scaffolds.

  • Nina-Louisa Efrém holds a Bachelor’s degree in Biochemistry from Freie Universität Berlin. She obtained her Master’s degree in Drug Design and Synthesis from Vrije Universiteit Amsterdam. After her studies, she participated in the Roche internship in Medicinal Chemistry (RiCH) program in Basel, Switzerland. Nina-Louisa joined the Medicinal Chemistry research group at the Leibniz Institute for Molecular Pharmacology as a PhD student in October 2021. Her projects focus on the development of tool compounds for SHP2 and for C-type lectin receptors. She is an Early-Stage Researcher within the Marie Skłodowska-Curie innovative training network ALLOstery in Drug Discovery (ALLODD).

  • Machoud got his bachelors degree in pharmaceutical sciences at Paris Descartes university between 2014 and 2017. After graduating as a pharmacist, he pursued with a masters degree in molecular chemistry at Sorbonne university in 2020. He did his Master thesis in the group of Prof. Dr. Craig Crews at Yale university followed by a one year industrial placement in the medicinal chemistry department at Roche in Basel before joining our group in 2021.

  • Axel studied biomedicinal Chemistry at the Johannes-Gutenberg University Mainz where he obtained his masters degree in 2020. He joined the Nazaré lab in the same year as a doctoral student. He is interested in drug design and synthesis and currently working on chemical probes and tool compounds for biomedicinal research.

  • Leonard works as PhD student in the research group of Dr. Marc Nazaré at the FMP Berlin since 2019. His research area focuses on the development of fluorescent probes in an interdisciplinary environment with collaboration partners from chemistry, biology and industry. Before pursuing a PhD, he studied „Molecular Life Science“ at the Friedrich-Alexander-University Erlangen-Nürnberg where he completed his Bachelor’s and Master’s thesis in the field of cancer-cell specific prodrugs and reactive oxygen species in the group of Prof. Andriy Mokhir. In his free time he is interested in everything around bicycles.

  • Giulia recently obtained her Master’s degree in Pharmaceutical Chemistry and Technology at the University of Milan. During her last academic year, she joined the Innovative Approaches in Medicinal Chemistry group, led by Prof. De Amici, where she focused on the synthesis of hybrid ligands for the muscarinic receptor M1. After obtaining her qualification for the profession of Pharmacist, she started an Erasmus Internship in the research group led by Dr. Marc Nazaré at the Leibniz Research Institute for Molecular Pharmacology. In addition to her passion for science, Giulia enjoys skiing, hiking, swimming, traveling, exploring diverse cultures, and immersing herself in various traditions around the world.

  • Désirée completed her Bachelor's degree in Chemistry at the Humboldt University of Berlin. She wrote her Bachelor's thesis in Hans Börner's working group on the modification of carrier materials using click chemistry. She also began her Master's degree in Chemistry at Humboldt University. As part of a research internship on single-molecule force spectroscopy measurements with mussel-inspired DOPA derivatives in the same working group, she completed an internship lasting several weeks at the University of California, Berkeley. For her master's thesis, she joined our group at the beginning of 2024 to deepen her knowledge in the field of medicinal chemistry. She is currently working on the development of covalent inhibitors of under-researched kinases with biomedical interest.

Alumni AG Nazaré
Dr. Carolina Vinagreiro
Jerome Paul
Dr. Peter Lindemann
Dr. Moníca Guberman
Dr. Małgorzata Wąsińska-Kałwa
Dr. Thais Gazzi
Dr. Benjamin Brennecke
Dr. Yelena Mostinski
Dr. Rana Alsalim
Dr. Murat Kucukdisli
Dr. Phani Kumar
Dr. Edgar Specker
Dr. Hassen Belabed
Jessica Przygodda
Dr. Vera Martos Riaño
Dr. André Horatscheck
Dr. María Isabel Fernández-Bachiller
Dr. Maria Pascual Lopez-Alberca
Dr. Upendra Rao Anumala
Sylvia Oestreich
Dr. Judith de Schryver (née Holz)
Lisa Teichmann
Marie Weise
Jens Schöne

Equipment


Agilent 1260 LC/DAD/TOF-MS (6530)

This analytical LCMS/TOF system is equipped with a binary pump (up to 5mL/min), a high performance wellplate sampler (0.1 - 100µL), a column oven (up to 100°C) and a diode array detector (80Hz) allowing for simultaneous measurement at wavelengths between 190 and 450nm. The backend is an Agilent 6530 Accurate Mass Q-ToF mass spectrometer enabling the user to determine the molecular composition of the analytes.

Agilent 1260 LC/DAD/ELSD/SQ-MS

Our Agilent InfinityLab LC/MSD XT system is equipped with an Agilent Infinity II 1260 DAD (80 Hz) and Agilent Infinity II 1290 ELSD for the detetction of UV-active as well as non UV-active analytes. The UHPLC module is linked to a single quadrupole (SQ) MS allowing for the detection of analytes with m/z up to 3000.

Agilent 1260 LC/DAD/SQ-MS (6120)

The analytical LCMS is equipped with a binary pump (up to 5mL/min), a high performance well plate sampler (0.1 - 40µL), a column oven and a new Agilent 1260 DAD (80 Hz) allowing for simultaneous measurement at wavelengths between 190 and 450nm. The backend is a robust single quadrupole mass spectrometer (up to 2000m/z). The system is used to analyze chemical reaction mixtures.

Agilent 1200 HPLC/DAD/ELSD

Our Agilent 1200 analytical HPLC is equipped with an autosampler, a column oven, a diode array detector (190-950nm) and an evaporative light scattering detector (Agilent 1260 Infinity ELSD) allowing for detection of non-UV absorbing analytes.

QTOF
Agilent 1260 LC/DAD/ELSD/SQ-MS
Picture of Agilent 1260 LC/DAD/SQ-MS (6120)
Picture of Agilent 1200 HPLC/DAD/ELSD

Agilent 1260 LC/DAD/TOF-MS (6530)

This analytical LCMS/TOF system is equipped with a binary pump (up to 5mL/min), a high performance wellplate sampler (0.1 - 100µL), a column oven (up to 100°C) and a diode array detector (80Hz) allowing for simultaneous measurement at wavelengths between 190 and 450nm. The backend is an Agilent 6530 Accurate Mass Q-ToF mass spectrometer enabling the user to determine the molecular composition of the analytes.

QTOF

Agilent 1260 LC/DAD/ELSD/SQ-MS

Our Agilent InfinityLab LC/MSD XT system is equipped with an Agilent Infinity II 1260 DAD (80 Hz) and Agilent Infinity II 1290 ELSD for the detetction of UV-active as well as non UV-active analytes. The UHPLC module is linked to a single quadrupole (SQ) MS allowing for the detection of analytes with m/z up to 3000.

Agilent 1260 LC/DAD/ELSD/SQ-MS

Agilent 1260 LC/DAD/SQ-MS (6120)

The analytical LCMS is equipped with a binary pump (up to 5mL/min), a high performance well plate sampler (0.1 - 40µL), a column oven and a new Agilent 1260 DAD (80 Hz) allowing for simultaneous measurement at wavelengths between 190 and 450nm. The backend is a robust single quadrupole mass spectrometer (up to 2000m/z). The system is used to analyze chemical reaction mixtures.

Picture of Agilent 1260 LC/DAD/SQ-MS (6120)

Agilent 1200 HPLC/DAD/ELSD

Our Agilent 1200 analytical HPLC is equipped with an autosampler, a column oven, a diode array detector (190-950nm) and an evaporative light scattering detector (Agilent 1260 Infinity ELSD) allowing for detection of non-UV absorbing analytes.

Picture of Agilent 1200 HPLC/DAD/ELSD

Preparative RP-HPLCs

For the separation of chemical reaction mixtures that are soluble in water/acetonitrile we use one of our prep RP-HPLC systems: a Gilson "PLC 2050" or Shimadzu "LC-20A Prominenc", respectively. Both are equipped with manual injection valves, multi wavelength detectors and fraction collection systems. The Gilson system also features an ELSD detector that facilitates the purification of non UV-active molecules.

Flash Chromatography

Our group has a total of four automated flash chromatography systems in use: a Biotage "Isolera One" and "Selekt" as well as two CombiFlash "Nextgen 300+". All are equipped with a binary pump systems, UV/Vis detection and automatic fraction collection, allowing for the automated separation and purification of UV active compounds in the milligram to multi gram scale. Additionally, the CombiFlash systems are equipped with ELS detection, allowing the convenient separation o

Lyophilizer Christ ALPHA 2-4 LSC

Our lyophilizer has 24 slots for the attachment of flasks. Sample solutions in suitable solvents like water or tert-butanol are frozen and the solvents are removed by vacuum sublimation.

Gilson RP-HPLC
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Picture

Preparative RP-HPLCs

For the separation of chemical reaction mixtures that are soluble in water/acetonitrile we use one of our prep RP-HPLC systems: a Gilson "PLC 2050" or Shimadzu "LC-20A Prominenc", respectively. Both are equipped with manual injection valves, multi wavelength detectors and fraction collection systems. The Gilson system also features an ELSD detector that facilitates the purification of non UV-active molecules.

Gilson RP-HPLC

Flash Chromatography

Our group has a total of four automated flash chromatography systems in use: a Biotage "Isolera One" and "Selekt" as well as two CombiFlash "Nextgen 300+". All are equipped with a binary pump systems, UV/Vis detection and automatic fraction collection, allowing for the automated separation and purification of UV active compounds in the milligram to multi gram scale. Additionally, the CombiFlash systems are equipped with ELS detection, allowing the convenient separation o

Bild

Lyophilizer Christ ALPHA 2-4 LSC

Our lyophilizer has 24 slots for the attachment of flasks. Sample solutions in suitable solvents like water or tert-butanol are frozen and the solvents are removed by vacuum sublimation.

Picture

Biotage Initiator+ Microwave with Robot Sixty Autosampler

For microwave syntheses we have two Biotage Initiator+ reactors available. They are equipped with a Robot Sixty autosampler systems which can take up to sixty samples each, with volumes between 0.2 mL to 20 mL.

Picture

Biotage Initiator+ Microwave with Robot Sixty Autosampler

For microwave syntheses we have two Biotage Initiator+ reactors available. They are equipped with a Robot Sixty autosampler systems which can take up to sixty samples each, with volumes between 0.2 mL to 20 mL.

Picture

Patents

Fluorescent probes for monoacylglycerol lipase (MAGL)
WO2021058443; Benz, J.; Gazzi, T.; Gobbi, L.; Grether, U.; Hornsperger, B.; Kroll, C.; Kuhn, B.; Mostinski, Y.; Nazaré, M.; O'Hara, F.; Richter, H.

Preparation of fused pyrimidinones as class II phosphoinositide 3-kinase inhibitors useful in treatment of diseases
WO2019234237A1; Lo, W.-T.; Belabed, H.; Haucke, V.; Nazare, M.; Kuecuekdisli, M.

1,2,4-Triazole derivatives as tankyrase inhibitors and their preparation
WO2019243822A1; Krauss, S.; Nazare, M.; Anumala, U. R.; Lehtio, L.; Waaler, J.; Wegert, A.; Leenders, R. G. G.

Preparation of triazole derivatives as tankyrase inhibitors useful in treatment and prevention of diseases
WO 2018118868; Krauss, S.; Nazare, M.; Anumala, U. R.; Lehtio, L.; Waaler, J.; Holsworth, D.; Wegert, A.; Leenders, R. G. G.