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:
PROTAC – a game changing technology.Konstantinidou M, Li J, Zhang B, Wang Z, Shaabani S, ter Brake F, Essa K, Dömling A; Expert Opinion Drug Discov. 2019; DOI:10.1080/17460441.2019.1659242
Glutarimide Alkaloids Through Multicomponent Reaction Chemistry.Konstantinidou M, Kurpiewska K, Kalinowska‐Tłuscik J, Dömling A; EurJOC, Vol. 2018 (47); Jul 19, 2019. DOI: 10.1002/ejoc.201801276E
1,3,4-Oxadiazoles by Ugi-tetrazole and Huisgen reactions. Wang Q, Mgimpatsang KC, Konstantinidou M, Shishkina SV, Dömling A; Org. Lett. 2019; DOI:10.1021/acs.orglett.9b02614
Pd-Catalyzed de novo assembly of diversely substituted indole-fused polyheterocycles. Konstantinidou M, Butera R, Mgimpatsang KC, Shishkina SV, Dömling A; J.Org. Chem. 2019; DOI: 10.1021/acs.joc.9b01258
Sequential multicomponent synthesis of 2-(imidazo[1,5-α]pyridin-1-yl)-1,3,4-oxadiazoles.Konstantinidou M, Sutanto F, Kurpiewska K, Kalinowska –Tłuścik J, Dömling A; Europ. J. Org. Chem. 2019, 10, 2029-2034; DOI: 10.1002/ejoc.201801880
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
List of posters:
Recent advances in heterocyclic synthesis via multi-component reaction schemes. EFMC International Symposium on Advances in Synthetic and Medicinal Chemistry (EFMC-ASMC), Sep 1-5, 2019, Athens, Greece
Inhibitors for Asp-proteases: anchor-based virtual screening, innovative chemistry and protein crystallography. Konstantinidou M, Magari F, Sutanto F, Ünver MY, Jumde VR, Camacho CJ, Klebe G, Hirsch AKH, Dömling A; ACS Spring National Meeting, Mar 31 - Apr 01, 2019, Orlando, USA
Discovery of unprecedented aspartic-protease inhibitors with applications in Alzheimer and other diseases.Konstantinidou M, Magari F, Sutanto F, Klebe G, Ünver MY, Jumde VR, Hirsch AKH, Dömling A; FIGON Dutch Medicine Days, Oct 01 -02, 2018
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, Sep 6-7, 2018, Ljubljana, Slovenia
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, Sep 2 - 6, 2018, Ljubljana, Slovenia
Glutarimide alkaloids via MCR chemistry. Konstantinidou M, Doemling A; 53rd International Conference on Medicinal Chemistry, RICT 2017, Jul 5 - 7, 2017, Toulouse, France
List of presentations:
Discovery of proteolysis targeting chimeras for leucine-rich repeat kinase 2 (LRRK2).
Konstantinidou M, Zhang B, Wang Z, de Brake F, Dolga A, Dömling A; New Frontiers in Structure-based Drug Design, Sept. 23-25, 2019, Florence, Italy
Applications of multi-component reaction chemistry in heterocyclic synthesis.
Konstantinidou M, Kurhade S, Sutanto F, Kurpiewska K, Kalinowska-Tłuscik J and Alexander Dömling A; ACS Spring National Meeting, Mar 31 - Apr 01, 2019, Orlando, USA
Tetrazole and oxadiazole heterocycles via multi-component reaction schemes.
Konstantinidou M, Kurhade S, Sutanto F, Kurpiewska K, Kalinowska-Tłuscik J and Alexander Dömling; AACS Fall National Meeting, Aug 25-29, 2019, San Diego, USA
Design of a multi-component reaction scaffold with inhibitory activity on aspartic proteases.
Konstantinidou M, Kurhade S, Sutanto F, Kurpiewska K, Kalinowska-Tłuscik J and Alexander Dömling; ACS Fall National Meeting, Aug 25-29, 2019, San Diego, USA
Discovery of unprecedented aspartic proteases inhibitors with applications in Alzheimer and other diseases.
Konstantinidou M, Sutanto F, Ünver MY, Jumde VR, Hirsch AKH, Magari F, Klebe G, Dömling A; 25th Young Research Fellow Meeting, SCT, Mar 5 - 7, 2018, Orleans, France
Design of MCR scaffold with inhibitory activity on aspartic proteases.
Konstantinidou M, Sutanto F, Magari F, Klebe G, Ünver MY, Jumde VR, Hirsch AKH, Dömling; AMCR 2018 , 7th International Conference on Multicomponent Reactions and Related Chemistry, Aug 26-31, 2018, Düsseldorf, Germany
Multicomponent reactions, applications in medical chemistry & new modalities in drug discovery.
Rijksuniversiteit Groningen, Feb 14, 2020, Groningen, the Netherlands
Department of Drug Design
School of Pharmacy
University of Groningen
Antonius Deusinglaan 1
9700 AD Groningen