Prof. Alex Dömling (RUG), Dr. Hongming Chen (AZ)
Design, synthesis and in vitro screening of novel molecules to control target proteins.
About the project:
The main focus of this project is the application of multicomponent-reaction chemistry (MCR) to biological targets. MCR chemistry enables the facile synthesis of scaffolds with high complexity and great diversity starting from simple or commercially available starting materials in one-pot reactions. I am currently using MCR chemistry towards the synthesis of natural products belonging to the class of glutarimide alkaloids. Novel scaffolds are also designed and synthesized aiming at the model enzyme called endothiapepsin. Furthermore, using fragments as starting points, MCR scaffolds are explored as potential stabilizers of the protein-protein interaction of 14-3-3 and p53. In each case the synthesized compounds are chosen rationally after creating virtual libraries and using tools for virtual screening.
I obtained the Degree in Pharmacy from the Aristotle University of Thessaloniki in 2012. In July 2014 I received my M.Sc. in Medicinal Chemistry from the same University under the supervision of Professor Hadjipavlou-Litina D. Shortly afterwards I was employed as a research assistant in the National Hellenic Research Foundation in Athens mainly dealing with the synthesis of dendrimers under the supervision of the Dr. G. Heropoulos and Dr. B. Steele. In February 2016, I joined as a PhD candidate the Drug Design Group in the University of Groningen under the guidance of Prof. A. Dömling.
AstraZeneca (3 months)
List of publications:
ß‐Carbolinone Analogues from the Ugi Silver Mine. Doemling A, Madhavachary R, Naveen N, Wang Y, Wang Q and Konstantinidou M; EurJoc, 17 April 2018: DOI: 10.1002/ejoc.201800557
Immune Checkpoint PD‐1/PD‐L1: Is There Life Beyond Antibodies? Konstantinidou M, Zarganes-Tzitzika T, Magiera-Mularz K, Holak TA and Dömling A, Angew. Chem., 2018, Vol. 57, Issue 18, 4840-4848. DOI: 10.1002/anie.201710407
Inhibitors of programmed cell death 1 (PD-1): a patent review (2010-2015), Zarganes-Tzitzikas T, Konstantinidou M, Gao Y, Krzemien D, Zak K, Dubin G, Holak TA, Dömling A, Expert Opin Ther Pat; 2016 Sep; 26 (9):973-7. Doi: 10.1080/13543776.2016.1206527
Sequential Multicomponent Synthesis of 2-(Imidazo[1,5-α]-pyridin-1-yl)-1,3,4-Oxadiazoles. Kurhade S, Konstantinidou M, Sutanto F, Kurpiewska K, Kalinowska-Tłuścik, Dömling A, Eur. J.Org.Chem. 2019, 2019-2034. DOI: 10.1002/ejoc.201801880
List of posters:
Glutarimide alkaloids via MCR chemistry. Konstantinidou M, Doemling A, 53rd International Conference on Medicinal Chemistry, RICT 2017, 5-7/7/2017, Toulouse, France
From fragment hits to MCR small molecules: design, synthesis and biological evaluation. Markella Konstantinidou, Fandi Sutanto, Francesca Magari, Gerhard Klebe, Muhammet Y. Ünver, Varsha R. Jumde, Anna K.H. Hirsch and Alexander Dömling, EFMC-ISMC 2018, XXV EFMC International Symposium on Medicinal Chemistry, 2-6/9/2018, Ljubljana, Slovenia
Design and synthesis of small molecules as protein-protein interaction stabilizers. Markella Konstantinidou, Zlata Boiarska, Dario Antonacci, Ave Kuusk, Hongming Chen, Christian Ottmann and Alexander Dömling, EFMC-YMCS 2018, 5th EFMC Young Medicinal Chemist Symposium Ljubljana, 6-7/9/2018, Ljubljana, Slovenia
List of presentations:
Discovery of unprecedented aspartic proteases inhibitors with applications in Alzheimer and other diseases, 25th Young Research Meeting, SCT, 5-7/3/2018, Orleans, France
Design of MCR scaffold with inhibitory activity on aspartic proteases, MCR 2018, 7th International Conference on Multicomponent Reactions and Related Chemistry, 26-31/8/2018, Düsseldorf, Germany
Department of Drug Design
School of Pharmacy
University of Groningen
Antonius Deusinglaan 1
9700 AD Groningen