Jürgen Vahter "Development of bisubstrate inhibitors for protein kinase CK2" | University of Tartu

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Contacts of UT units

Faculty of Arts and Humanities
Faculty phone: 
+372 737 5341
Faculty address: 
Jakobi 2, rooms 116–121, 51005 Tartu
  • Dean's Office
    Faculty phone: 
    + 372 737 5341
    Faculty address: 
    Jakobi 2, rooms 116–121, 51005 Tartu
  • Institute of History and Archaeology
    Faculty phone: 
    +372 737 5651
    Faculty address: 
    Jakobi 2, 51005 Tartu
  • Institute of Estonian and General Linguistics
    Faculty phone: 
    +372 737 5221
    Faculty address: 
    Jakobi 2, 51005 Tartu
  • Institute of Philosophy and Semiotics
    Faculty phone: 
    +372 737 5314
    Faculty address: 
    Jakobi 2, rooms 309–352, 51005 Tartu
  • Institute of Cultural Research
    Faculty phone: 
    (+372) 737 5223
    Faculty address: 
    Ülikooli 16, 51003 Tartu
  • School of Theology and Religious Studies
    Faculty phone: 
    +372 737 5301
    Faculty address: 
    Ülikooli 18–310, 50090 Tartu
  • College of Foreign Languages and Cultures
    Faculty address: 
    Lossi 3, 51003 Tartu
  • Viljandi Culture Academy
    Faculty phone: 
    +372 435 5232
    Faculty address: 
    Posti 1, 71004 Viljandi
Faculty of Social Sciences
Faculty phone: 
+372 737 5957
Faculty address: 
Lossi 36, 51003 Tartu
  • Dean's Office
    Faculty phone: 
    + 372 737 5900
    Faculty address: 
    Lossi 36, 51003 Tartu
  • Institute of Education
    Faculty phone: 
    +372 737 6440
    Faculty address: 
    Salme 1a–29, 50103 Tartu
  • Johan Skytte Institute of Political Studies
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    +372 737 5582
    Faculty address: 
    Lossi 36–301, 51003 Tartu
  • School of Economics and Business Administration
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    J. Liivi 4, 50409 Tartu
  • Institute of Psychology
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    Näituse 2, 50409 Tartu
  • School of Law
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  • Institute of Social Studies
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Faculty of Medicine
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  • Dean's Office
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    Ravila 19, 50411 Tartu
  • Institute of Biomedicine and Translational Medicine
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    Biomeedikum, Ravila 19, 50411 Tartu
  • Institute of Pharmacy
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  • Institute of Dentistry
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  • Institute of Clinical Medicine
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    Ravila 19, 50411 Tartu
  • Institute of Sport Sciences and Physiotherapy
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    Faculty address: 
    Jakobi 5–205, 51005 Tartu
Faculty of Science and Technology
Faculty phone: 
+372 737 5820
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Vanemuise 46–208, 51014 Tartu
  • Dean's Office
    Faculty phone: 
    +372 737 5820
    Faculty address: 
    Vanemuise 46–208, 51005 Tartu
  • Institute of Computer Science
    Faculty phone: 
    +372 737 5445
    Faculty address: 
    J. Liivi 2, 50409 Tartu
  • Estonian Marine Institute
    Faculty phone: 
    +372 671 8902
    Faculty address: 
    Mäealuse 14, 12618 Tallinn
  • Institute of Physics
    Faculty address: 
    W. Ostwaldi 1, 50411 Tartu
  • Institute of Chemistry
    Faculty phone: 
    +372 737 5261
    Faculty address: 
    Ravila 14a, 50411 Tartu
  • Institute of Mathematics and Statistics
    Faculty phone: 
    +372 737 5860
    Faculty address: 
    J. Liivi 2, 50409 Tartu
  • Institute of Molecular and Cell Biology
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    Riia 23, 23b–134, 51010 Tartu
  • Tartu Observatory
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    Observatooriumi 1, Tõravere, 61602 Tartumaa
  • Institute of Technology
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    Faculty address: 
    Nooruse 1, 50411 Tartu
  • Institute of Ecology and Earth Sciences
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    Faculty address: 
    Vanemuise 46, 51003 Tartu
Institutions
  • Library
    Faculty phone: 
    +372 737 5702
    Faculty address: 
    W. Struve 1, 50091 Tartu
  • Youth Academy
    Faculty phone: 
    +372 737 5581
    Faculty address: 
    Uppsala 10, 51003 Tartu
  • Institute of Genomics
    Faculty phone: 
    +372 737 4000
    Faculty address: 
    Riia 23b, 51010 Tartu
  • Museum
    Faculty phone: 
    +372 737 5674
    Faculty address: 
    Lossi 25, 51003 Tartu
  • University of Tartu Natural History Museum and Botanical Garden
    Faculty phone: 
    +372 737 6076
    Faculty address: 
    Vanemuise 46, 51003 Tartu
Support Units
  • Administrative Office
    Faculty phone: 
    +372 737 5606
    Faculty address: 
    Ülikooli 18a, 51005 Tartu
  • Centre for Entrepreneurship and Innovation
    Faculty phone: 
    +372 737 6339
    Faculty address: 
    Lossi 3, III floor, 51003 Tartu
  • University Office in Tallinn
    Faculty phone: 
    +372 737 6600
    Faculty address: 
    Teatri väljak 3, 10143 Tallinn
  • Estates Office
    Faculty phone: 
    +372 737 5137
    Faculty address: 
    Ülikooli 18a, 51005 Tartu
  • Finance Office
    Faculty phone: 
    +372 737 5125
    Faculty address: 
    Jakobi 4, 51005 Tartu
  • Grant Office
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    +372 737 6215
    Faculty address: 
    Lossi 3, III floor, 51003 Tartu
  • Information Technology Office
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    Faculty address: 
    Ülikooli 18a, 51005 Tartu
  • Human Resources Office
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    +372 737 5145
    Faculty address: 
    Ülikooli 18, rooms 302 and 304, 50090 Tartu
  • Internal Audit Office
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    Ülikooli 17–103, 51005 Tartu
  • Marketing and Communication Office
    Faculty phone: 
    +372 737 5687
    Faculty address: 
    Ülikooli 18, rooms 102, 104, 209, 210, 50090 Tartu
  • Office of Academic Affairs
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    +372 737 5620
    Faculty address: 
    Ülikooli 18, 50090 Tartu
  • Procurement Office
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    +372 737 6632
    Faculty address: 
    Ülikooli 18a, 51005 Tartu
  • Rector's Strategy Office
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    Faculty address: 
    Ülikooli 18, 50090 Tartu
  • Student Council
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    Faculty address: 
    Ülikooli 18b, 51005 Tartu
Other Units
  • University of Tartu Academic Sports Club
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    +372 737 5371
    Faculty address: 
    Ujula 4, 51008 Tartu
  • Tartu Student Village
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  • Tartu Students’ Club
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    Faculty address: 
    Kalevi 24, 51010 Tartu
  • University of Tartu Press
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    Faculty address: 
    W. Struve 1, 50091 Tartu
  • Tartu University Hospital
    Faculty address: 
    L. Puusepa 1a, 50406 Tartu
  • University of Tartu Foundation
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    +372 737 5852
    Faculty address: 
    Ülikooli 18, 50090 Tartu
  • View all other units

Jürgen Vahter "Development of bisubstrate inhibitors for protein kinase CK2"

Date: 
14.03.2019 - 14:00

On 14 March at 14 Jürgen Vahter will defend his doctoral thesis „Development of bisubstrate inhibitors for protein kinase CK2”.

Supervisor:
Lecturer Erki Enkvist  (PhD), Institute of Chemisrty, University of Tartu

Opponent:
Prof. Joachim Jose (PhD), University of Münster, Germany

Summary:
Protein kinases (PKs) are a protein superfamily having more than 530 enzymes. Protein kinases are transferases that catalyze the transfer of the terminal phosphoryl group from nucleoside triphosphates to target substrate proteins/peptides, which thereafter change of activaty. Since protein kinases have important rolls in cell regulation, it has been found that misregulation of the signal transduction networks of kinases has shown to be related with different diseases and that is why many of protein kinases are target molecules of novel drugs and for compounds in current drug development. By now there are 48 FDA (Food and Drug Administration) approved protein kinase inhibitors used in treatment of different diseases.

One of the members of protein kinase family is CK2, which is responsible of about 10% of all protein phosphorylations in cells. Because of the overexpression and elevated activity of CK2 and unbalanced expression of its subunits, CK2 is reported to be related to number of different diseases but is mostly associated with different types of cancers. Throughout the years many ATP-competitive inhibitors have developed for CK2 that bind to the ATP binding site and restrain the normal functioning of the enzyme. Since most of the protein kinases use ATP as the source of the phosphoryl group, this type of inhibitors have problem with substrate selectivity.

During this work, bisubstrate inhibitors were developed for the protein kinase CK2. Bisubstrate inhibitors bind simultaneously to both active sites (ATP and protein substrate binding sites) of the enzyme. Bisubstrate inhibitors consist of an ATP-competitive moiety, a protein substrate mimic and a linker. Turing the development of the inhibitors, four different ATP-competitive fragments were used: previously known CK2 inhibitors TBBi and CX-4945 and 4-(2-amino-1,3-thiazol-5-yl)benzoic acid (ATB) and its selenium-containing counterpart, which both possessed long lifetime luminescence properties. In addition to these variations, also the length of protein substrate mimetic and the composition and length of the linker were optimized. Some of the inhibitors were also conjugated with fluorescence dyes. As a result of this research, novel CK2 inhibitors with higher binding affinity and also better selectivity toward the target enzyme were synthesized. These inhibitors allow to measure the activity of the CK2 and characterize novel, potent inhibitors of CK2. Also, compounds possessing long lifetime luminescence properties have advantages  in biological samples, where the time gated measurements eliminate the autofluorescence background of biological components and leads to higher signal sensitivity.

 

Location: 
Ravila 14A-1020
Event category: