TY - JOUR AU - Kollár, Levente AU - Grabrijan, Katarina AU - Hrast Rambaher, Martina AU - Bozovičar, Krištof AU - Imre, Tímea AU - Ferenczy, György AU - Gobec, Stanislav AU - Keserű, György Miklós TI - Boronic acid inhibitors of penicillin-binding protein 1b: serine and lysine labelling agents JF - JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY J2 - J ENZYM INHIB MED CH VL - 39 PY - 2024 IS - 1 SN - 1475-6366 DO - 10.1080/14756366.2024.2305833 UR - https://m2.mtmt.hu/api/publication/34718013 ID - 34718013 N1 - Medicinal Chemistry Research Group, Research Centre for Natural Sciences, Budapest, Hungary Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Budapest, Hungary Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia MS Metabolomics Research Group, Research Centre for Natural Sciences, Budapest, Hungary Export Date: 8 March 2024 CODEN: JEIMA Correspondence Address: Keserű, G.M.; Department of Organic Chemistry and Technology, Műegyetem rkp. 3., Hungary; email: keseru.gyorgy@ttk.hu Funding details: RRF-2.3.1-21-2022-00015 Funding details: Javna Agencija za Raziskovalno Dejavnost RS, ARRS, N1-0169, P1-0208 Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFI, K135335 Funding details: Richter Gedeon Talentum Alapítvány Funding text 1: We thank Dr. Andrea Dessen (IBS, Grenoble) for donation of PBP1b plasmid and Dr. Pál Szabó for HRMS measurements. This study was supported by National Research, Development and Innovation Office Grants K135335, and by the National Drug Research and Development Laboratory (PharmaLab) project (RRF-2.3.1-21-2022-00015). Funding text 2: This research was funded by the National Research Development and Innovation Office (Grant Numbers: SNN 135335), Slovenian Research Agency (ARRS) Research Core Funding P1-0208, grant N1-0169 and a PhD grant to K.G. L.K. is supported by the Gedeon Richter Talentum Foundation and the József Varga Foundation and Javna Agencija za Raziskovalno Dejavnost RS. We thank Dr. Andrea Dessen (IBS, Grenoble) for donation of PBP1b plasmid and Dr. Pál Szabó for HRMS measurements. This study was supported by National Research, Development and Innovation Office Grants K135335, and by the National Drug Research and Development Laboratory (PharmaLab) project (RRF-2.3.1-21-2022-00015). LA - English DB - MTMT ER - TY - JOUR AU - Mihalovits, Levente Márk AU - Kollár, Levente AU - Bajusz, Dávid AU - Knez, Damijan AU - Bozovičar, Krištof AU - Imre, Timea AU - Ferenczy, György AU - Gobec, Stanislav AU - Keserű, György Miklós TI - Molecular Mechanism of Labelling Functional Cysteines by Heterocyclic Thiones JF - CHEMPHYSCHEM: A EUROPEAN JOURNAL OF CHEMICAL PHYSICS AND PHYSICAL CHEMISTRY J2 - CHEMPHYSCHEM VL - 25 PY - 2024 IS - 1 SN - 1439-4235 DO - 10.1002/cphc.202300596 UR - https://m2.mtmt.hu/api/publication/34223252 ID - 34223252 N1 - Medicinal Chemistry Research Group, HUN-REN Research Centre for Natural Sciences, Magyar tudósok krt. 2, Budapest, 1117, Hungary Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3., Budapest, 1111, Hungary Department of Medicinal Chemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, Ljubljana, 1000, Slovenia Department of Pharmaceutical Biology, Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, Ljubljana, 1000, Slovenia MS Metabolomics Research Group, HUN-REN Research Centre for Natural Sciences, Magyar tudósok krt. 2, Budapest, 1117, Hungary Export Date: 24 November 2023 CODEN: CPCHF Correspondence Address: Bajusz, D.; Medicinal Chemistry Research Group, Magyar tudósok krt. 2, Hungary; email: bajusz.david@ttk.hu Correspondence Address: Keserű, G.M.; Medicinal Chemistry Research Group, Magyar tudósok krt. 2, Hungary; email: keseru.gyorgy@ttk.hu AB - Heterocyclic thiones have recently been identified as reversible covalent warheads, consistent with their mild electrophilic nature. Little is known so far about their mechanism of action in labelling nucleophilic sidechains, especially cysteines. The vast number of tractable cysteines promotes a wide range of target proteins to examine; however, our focus was put on functional cysteines. We chose the main protease of SARS‐CoV‐2 harboring Cys145 at the active site that is a structurally characterized and clinically validated target of covalent inhibitors. We screened an in‐house, cysteine‐targeting covalent inhibitor library which resulted in several covalent fragment hits with benzoxazole, benzothiazole and benzimidazole cores. Thione derivatives and Michael acceptors were selected for further investigations with the objective of exploring the mechanism of inhibition of the thiones and using the thoroughly characterized Michael acceptors for benchmarking our studies. Classical and hybrid quantum mechanical/molecular mechanical (QM/MM) molecular dynamics simulations were carried out that revealed a new mechanism of covalent cysteine labelling by thione derivatives, which was supported by QM and free energy calculations and by a wide range of experimental results. Our study shows that the molecular recognition step plays a crucial role in the overall binding of both sets of molecules. LA - English DB - MTMT ER - TY - JOUR AU - Németh, András György AU - Kollár, Levente AU - Németh, K. AU - Schlosser, Gitta (Vácziné) AU - Minus, Annamária AU - Keserű, György Miklós TI - On-DNA Synthesis of Multisubstituted Indoles JF - ORGANIC LETTERS J2 - ORG LETT PY - 2024 PG - 6 SN - 1523-7060 DO - 10.1021/acs.orglett.3c03602 UR - https://m2.mtmt.hu/api/publication/34492242 ID - 34492242 N1 - Export Date: 10 January 2024; Cited By: 0; Correspondence Address: G.M. Keserű; Medicinal Chemistry Research Group, HUN-REN Research Centre for Natural Sciences, Budapest, H-1117, Hungary; email: keseru.gyorgy@ttk.hu; CODEN: ORLEF AB - The increasing role of the DNA-encoded library technology in early phase drug discovery represents a significant demand for DNA-compatible synthetic methods for therapeutically relevant heterocycles. Herein, we report the first on-DNA synthesis of multisubstituted indoles via a cascade reaction of Sonogashira coupling and intramolecular ring closure. Further functionalization by Suzuki coupling at the third position exploits a diverse chemical space. The high fidelity of the method also enabled the construction of an indole-based mock library. © 2023 The Authors. Published by American Chemical Society. LA - English DB - MTMT ER - TY - JOUR AU - Kollár, Levente AU - Gobec, Martina AU - Proj, Matic AU - Smrdel, Lara AU - Knez, Damijan AU - Imre, Timea AU - Gömöry, Ágnes AU - Petri, László AU - Ábrányi-Balogh, Péter AU - Csányi, Dorottya AU - Ferenczy, György AU - Gobec, Stanislav AU - Sosič, Izidor AU - Keserű, György Miklós TI - Fragment-Sized and Bidentate (Immuno)Proteasome Inhibitors Derived from Cysteine and Threonine Targeting Warheads JF - CELLS J2 - CELLS-BASEL VL - 10 PY - 2021 IS - 12 PG - 19 SN - 2073-4409 DO - 10.3390/cells10123431 UR - https://m2.mtmt.hu/api/publication/32544488 ID - 32544488 N1 - Medicinal Chemistry Research Group, Research Centre for Natural Sciences, Magyar tudósok krt. 2, Budapest, H-1117, Hungary Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, Ljubljana, SI-1000, Slovenia MS Metabolomics Research Group, Research Centre for Natural Sciences, Magyar tudósok krt. 2, Budapest, H-1117, Hungary MS Proteomics Research Group, Research Centre for Natural Sciences, Magyar tudósok krt. 2, Budapest, H-1117, Hungary Export Date: 27 May 2022 Correspondence Address: Sosič, I.; Faculty of Pharmacy, Aškerčeva cesta 7, Slovenia; email: izidor.sosic@ffa.uni-lj.si Correspondence Address: Keserű, G.M.; Medicinal Chemistry Research Group, Magyar tudósok krt. 2, Hungary; email: keseru.gyorgy@ttk.hu LA - English DB - MTMT ER - TY - JOUR AU - Kollár, Levente AU - Ferenczy, György AU - Proj, Matic AU - Gobec, Martina AU - Gobec, Stanislav AU - Sosič, Izidor AU - Keserű, György Miklós TI - Virtual Screening and Biochemical Testing of Borocycles as Immunoproteasome Inhibitors JF - PERIODICA POLYTECHNICA-CHEMICAL ENGINEERING J2 - PERIOD POLYTECH CHEM ENG VL - 65 PY - 2021 IS - 3 SP - 292 EP - 298 PG - 7 SN - 0324-5853 DO - 10.3311/PPch.17202 UR - https://m2.mtmt.hu/api/publication/32129052 ID - 32129052 LA - English DB - MTMT ER - TY - JOUR AU - Kollár, Levente AU - Gobec, Martina AU - Szilágyi, Bence AU - Proj, Matic AU - Knez, Damijan AU - Ábrányi-Balogh, Péter AU - Petri, László AU - Imre, Timea AU - Bajusz, Dávid AU - Ferenczy, György AU - Gobec, Stanislav AU - Keserű, György Miklós AU - Sosič, Izidor TI - Discovery of selective fragment-sized immunoproteasome inhibitors JF - EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY J2 - EUR J MED CHEM VL - 219 PY - 2021 PG - 23 SN - 0223-5234 DO - 10.1016/j.ejmech.2021.113455 UR - https://m2.mtmt.hu/api/publication/31984014 ID - 31984014 LA - English DB - MTMT ER -