Antonis Drakopoulos, University of Guthenburg

Antonis Drakopoulos, PhD

• Education

10/2005 – 12/2011 - Diploma in Pharmacy - University of Athens, Greece
09/2012 -  License to practice
10/2012 – 11/2014 - M.Phil. in Synthetic Pharmaceutical Chemistry -University of Athens, Greece
12/2014 – 06/2020 - PhD in Chemical Biology -University of Würzburg, Germany

• Experience

My first research project was done while I was a diploma student at the NCSR “Democritus”, Athens, Greece (10/2009 – 09/2010), where I worked on the synthesis of technetium and rhenium radiopharmaceutical coordination compounds. My M.Phil. thesis focused on the design, synthesis, and characterization of influenza antiviral aminoadamantane derivatives and in silico methods to study the mechanism of action of the M2 viral protein. Also, during my M.Phil. I was awarded an IKYDA 2013 exchange fellowship for a short research stay at the University of Düsseldorf, Germany.

My PhD focused on developing subtype-selective fluorescent probes for the study of opioid receptor oligomerization using Single Molecule Microscopy techniques. The project was an integrated part of the International Doctoral Program “Receptor Dynamics” funded by the Elite Network of Bavaria. I prepared, purified and characterised the probes in the group of Prof. M. Decker at the University of Würzburg, Germany, and performed cell cultures and microscopy assays in the group of Prof. D. Calebiro at the University of Birmingham, UK during a 4-month research stay abroad (23/07-01/12/2018). A poster describing part of this work was awarded a prize in the 6th EFMC Young Medicinal Chemist Symposium in 2019. After my doctoral promotion, I worked for NovaMechanics Ltd., based in Cyprus, as a computational chemist (07/01 – 30/09/2021), thus gaining experience in an industrial R&D environment. Moreover, through this position I participated in the MSCA-RISE program “EthnoHERBS” and did a 4-month secondment (19/05 – 19/09/2021) in the Department of Biology, University of Minho, Portugal, investigating natural products and plant extracts as prospective medicaments against skin disorders. In my free time, I enjoy playing guitar and baglamas, homebrewing beer, reading and discussing philosophy, and taking long walks with friends.

Protein kinases (PKs) are involved in many cellular functions, including proliferation, differentiation, migration, and host–pathogen interactions and are an important class of drug targets. Labelling of PKs inside living cells is of great importance in the characterisation of PK dynamics, mobility, and function. In this project, I will develop a novel labelling method for kinases based on ligand-directed affinity labelling principles. In this labelling method, a selective and ATP-competitive kinase inhibitor that binds to the target kinase is attached through a linker to a tag group that can covalently attach to a residue near the ATP binding site. This tag may be functionalised with any cargo (e.g. a fluorophore, ligands for proteolysis targeting chimaera [PROTAC], etc.) by click chemistry. Bruton’s tyrosine kinase (BTK) will serve as an initial showcase for this strategy, which should be applicable to many kinases. BTK is an emerging therapeutic target for several malignancies, including leukaemia and lymphoma.

By taking advantage of existing BTK inhibitor structure-activity relationships and trialling a variety of suitable 'inverted' warheads (electrophilic groups that will selectively react with a specific residue in the kinase), the tag is envisaged to be covalently attached to the enzyme, while the ligand that binds to the ATP binding site will be released and can diffuse away from the kinase. Thus, the kinase should remain enzymatically active after the labelling. Computational chemistry techniques will be employed to facilitate a rational probe design, including warhead reactivity, linker length as well as setting synthetic priorities. This work will be supported by an external secondment to AstraZeneca, for collaboration with world-leading computational chemists such as Dr. Peter Brandt. Synthesis, analysis, structure elucidation, testing, and validation of the probes will be conducted in the group of Prof. Morten Grøtli at the University of Gothenburg, Sweden who is an expert on kinase inhibitors.

Finally, the probes will be used to measure BTK levels in lung cancer cells and to investigate how BTK levels affect p53 status and tumour viability. This final part of the project includes an internal academic secondment in the group of Prof. Ana Janic at Pompeu Fabra University, Barcelona, Spain, a leading cancer expert.