@article{MTMT:35160281,
	title = {Mapping protein binding sites by photoreactive fragment pharmacophores},
	url = {https://m2.mtmt.hu/api/publication/35160281},
	author = {Ábrányi-Balogh, Péter and Bajusz, Dávid and Orgován, Zoltán and Keeley, Aaron Brian and Petri, László and Péczka, Nikolett and Szalai, Tibor Viktor and Pálfy, Gyula and Gadanecz, Márton and Grant, Emma K. and Imre, Tímea and Takács, Tamás and Randelovic, Ivan and Baranyi, Marcell and Marton, András Dénes and Schlosser, Gitta (Vácziné) and Ashraf, Qirat F. and de Araujo, Elvin D. and Karancsi, Tamás and Buday, László and Tóvári, József and Perczel, András and Bush, Jacob T. and Keserű, György Miklós},
	doi = {10.1038/s42004-024-01252-w},
	journal-iso = {COMMUN CHEM},
	journal = {COMMUNICATIONS CHEMISTRY},
	volume = {7},
	unique-id = {35160281},
	issn = {2399-3669},
	abstract = {Fragment screening is a popular strategy of generating viable chemical starting points especially for challenging targets. Although fragments provide a better coverage of chemical space and they have typically higher chance of binding, their weak affinity necessitates highly sensitive biophysical assays. Here, we introduce a screening concept that combines evolutionary optimized fragment pharmacophores with the use of a photoaffinity handle that enables high hit rates by LC-MS-based detection. The sensitivity of our screening protocol was further improved by a target-conjugated photocatalyst. We have designed, synthesized, and screened 100 diazirine-tagged fragments against three benchmark and three therapeutically relevant protein targets of different tractability. Our therapeutic targets included a conventional enzyme, the first bromodomain of BRD4, a protein-protein interaction represented by the oncogenic KRas G12D protein, and the yet unliganded N -terminal domain of the STAT5B transcription factor. We have discovered several fragment hits against all three targets and identified their binding sites via enzymatic digestion, structural studies and modeling. Our results revealed that this protocol outperforms screening traditional fully functionalized and photoaffinity fragments in better exploration of the available binding sites and higher hit rates observed for even difficult targets.},
	year = {2024},
	eissn = {2399-3669},
	orcid-numbers = {Bajusz, Dávid/0000-0003-4277-9481; Pálfy, Gyula/0000-0003-1590-5331; Gadanecz, Márton/0009-0009-8076-7597; Grant, Emma K./0009-0005-5229-9125; Randelovic, Ivan/0000-0003-0161-0022; Schlosser, Gitta (Vácziné)/0000-0002-7637-7133; de Araujo, Elvin D./0000-0003-0716-2830; Tóvári, József/0000-0002-5543-3204; Perczel, András/0000-0003-1252-6416; Bush, Jacob T./0000-0001-7165-0092}
}

@article{MTMT:34445373,
	title = {Electrophilic MiniFrags Revealed Unprecedented Binding Sites for Covalent HDAC8 Inhibitors},
	url = {https://m2.mtmt.hu/api/publication/34445373},
	author = {Keeley, Aaron Brian and Kopranovic, Aleksandra and Di Lorenzo, Vincenzo and Ábrányi-Balogh, Péter and Jänsch, Niklas and Lai, Linh N. and Petri, László and Orgován, Zoltán and Pölöske, Daniel and Orlova, Anna and Németh, András György and Desczyk, Charlotte and Imre, Timea and Bajusz, Dávid and Moriggl, Richard and Meyer-Almes, Franz-Josef and Keserű, György Miklós},
	doi = {10.1021/acs.jmedchem.3c01779},
	journal-iso = {J MED CHEM},
	journal = {JOURNAL OF MEDICINAL CHEMISTRY},
	volume = {67},
	unique-id = {34445373},
	issn = {0022-2623},
	abstract = {Screening of ultra-low-molecular weight ligands (MiniFrags) successfully identified viable chemical starting points for a variety of drug targets. Here we report the electrophilic analogues of MiniFrags that allow the mapping of potential binding sites for covalent inhibitors by biochemical screening and mass spectrometry. Small electrophilic heterocycles and their N-quaternized analogues were first characterized in the glutathione assay to analyze their electrophilic reactivity. Next, the library was used for systematic mapping of potential covalent binding sites available in human histone deacetylase 8 (HDAC8). The covalent labeling of HDAC8 cysteines has been proven by tandem mass spectrometry measurements, and the observations were explained by mutating HDAC8 cysteines. As a result, screening of electrophilic MiniFrags identified three potential binding sites suitable for the development of allosteric covalent HDAC8 inhibitors. One of the hit fragments was merged with a known HDAC8 inhibitor fragment using different linkers, and the linker length was optimized to result in a lead-like covalent inhibitor. © 2023 The Authors. Published by American Chemical Society},
	year = {2024},
	eissn = {1520-4804},
	pages = {572-585},
	orcid-numbers = {Di Lorenzo, Vincenzo/0000-0002-3140-3561; Bajusz, Dávid/0000-0003-4277-9481; Meyer-Almes, Franz-Josef/0000-0002-1001-3249}
}

@article{MTMT:34718013,
	title = {Boronic acid inhibitors of penicillin-binding protein 1b: serine and lysine labelling agents},
	url = {https://m2.mtmt.hu/api/publication/34718013},
	author = {Kollár, Levente and Grabrijan, Katarina and Hrast Rambaher, Martina and Bozovičar, Krištof and Imre, Tímea and Ferenczy, György and Gobec, Stanislav and Keserű, György Miklós},
	doi = {10.1080/14756366.2024.2305833},
	journal-iso = {J ENZYM INHIB MED CH},
	journal = {JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY},
	volume = {39},
	unique-id = {34718013},
	issn = {1475-6366},
	year = {2024},
	eissn = {1475-6374},
	orcid-numbers = {Ferenczy, György/0000-0002-5771-4616}
}

@article{MTMT:34720633,
	title = {Novel-Type GABA B PAMs: Structure–Activity Relationship in Light of the Protein Structure},
	url = {https://m2.mtmt.hu/api/publication/34720633},
	author = {Krámos, Balázs and Hadady, Zsuzsa and Makó, Attila and Szántó, Gábor and Felföldi, Nóra and Magdó, Ildikó and Bobok, Amrita Ágnes and Bata, Imre and Román, Viktor and Visegrády, András and Keserű, György Miklós and Greiner, István and Éles, János},
	doi = {10.1021/acsmedchemlett.3c00560},
	journal-iso = {ACS MED CHEM LETT},
	journal = {ACS MEDICINAL CHEMISTRY LETTERS},
	unique-id = {34720633},
	issn = {1948-5875},
	year = {2024},
	orcid-numbers = {Krámos, Balázs/0000-0002-6387-7382; Greiner, István/0000-0002-5336-2828; Éles, János/0000-0001-9185-1123}
}

@{MTMT:34535308,
	title = {Free Energy Calculations in Covalent Drug Design},
	url = {https://m2.mtmt.hu/api/publication/34535308},
	author = {Mihalovits, Levente Márk and Ferenczy, György and Keserű, György Miklós},
	booktitle = {Computational Drug Discovery},
	doi = {10.1002/9783527840748.ch23},
	unique-id = {34535308},
	year = {2024},
	pages = {561-578},
	orcid-numbers = {Mihalovits, Levente Márk/0000-0003-1022-3294; Ferenczy, György/0000-0002-5771-4616}
}

@article{MTMT:34223252,
	title = {Molecular Mechanism of Labelling Functional Cysteines by Heterocyclic Thiones},
	url = {https://m2.mtmt.hu/api/publication/34223252},
	author = {Mihalovits, Levente Márk and Kollár, Levente and Bajusz, Dávid and Knez, Damijan and Bozovičar, Krištof and Imre, Timea and Ferenczy, György and Gobec, Stanislav and Keserű, György Miklós},
	doi = {10.1002/cphc.202300596},
	journal-iso = {CHEMPHYSCHEM},
	journal = {CHEMPHYSCHEM: A EUROPEAN JOURNAL OF CHEMICAL PHYSICS AND PHYSICAL CHEMISTRY},
	volume = {25},
	unique-id = {34223252},
	issn = {1439-4235},
	abstract = {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.},
	year = {2024},
	eissn = {1439-7641},
	orcid-numbers = {Mihalovits, Levente Márk/0000-0003-1022-3294; Bajusz, Dávid/0000-0003-4277-9481; Ferenczy, György/0000-0002-5771-4616}
}

@article{MTMT:35265081,
	title = {Progress on the development of Class A GPCR‐biased ligands},
	url = {https://m2.mtmt.hu/api/publication/35265081},
	author = {Morales, Paula and Scharf, Magdalena M. and Bermudez, Marcel and Egyed, Attila and Franco, Rafael and Hansen, Olivia K. and Jagerovic, Nadine and Jakubík, Jan and Keserű, György Miklós and Kiss, Dóra Judit and Kozielewicz, Pawel and Larsen, Olav and Majellaro, Maria and Mallo‐Abreu, Ana and Navarro, Gemma and Prieto‐Díaz, Rubén and Rosenkilde, Mette M. and Sotelo, Eddy and Stark, Holger and Werner, Tobias and Wingler, Laura M.},
	doi = {10.1111/bph.17301},
	journal-iso = {BR J PHARMACOL},
	journal = {BRITISH JOURNAL OF PHARMACOLOGY},
	unique-id = {35265081},
	issn = {0007-1188},
	abstract = {Class A G protein‐coupled receptors (GPCRs) continue to garner interest for their essential roles in cell signalling and their importance as drug targets. Although numerous drugs in the clinic target these receptors, over 60% GPCRs remain unexploited. Moreover, the adverse effects triggered by the available unbiased GPCR modulators, limit their use and therapeutic value. In this context, the elucidation of biased signalling has opened up new pharmacological avenues holding promise for safer therapeutics. Functionally selective ligands favour receptor conformations facilitating the recruitment of specific effectors and the modulation of the associated pathways. This review surveys the current drug discovery landscape of GPCR‐biased modulators with a focus on recent advances. Understanding the biological effects of this preferential coupling is at different stages depending on the Class A GPCR family. Therefore, with a focus on individual GPCR families, we present a compilation of the functionally selective modulators reported over the past few years. In doing so, we dissect their therapeutic relevance, molecular determinants and potential clinical applications.},
	year = {2024},
	eissn = {1476-5381},
	orcid-numbers = {Scharf, Magdalena M./0000-0002-3305-3956; Bermudez, Marcel/0000-0002-7421-3282; Franco, Rafael/0000-0003-2549-4919; Jakubík, Jan/0000-0002-1737-1487; Kozielewicz, Pawel/0000-0003-1414-3566; Navarro, Gemma/0000-0003-4654-0873; Rosenkilde, Mette M./0000-0001-9600-3254; Stark, Holger/0000-0003-3336-1710}
}

@article{MTMT:34492242,
	title = {On-DNA Synthesis of Multisubstituted Indoles},
	url = {https://m2.mtmt.hu/api/publication/34492242},
	author = {Németh, András György and Kollár, Levente and Németh, K. and Schlosser, Gitta (Vácziné) and Minus, Annamária and Keserű, György Miklós},
	doi = {10.1021/acs.orglett.3c03602},
	journal-iso = {ORG LETT},
	journal = {ORGANIC LETTERS},
	volume = {26},
	unique-id = {34492242},
	issn = {1523-7060},
	abstract = {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.},
	year = {2024},
	eissn = {1523-7052},
	pages = {2517-2522},
	orcid-numbers = {Schlosser, Gitta (Vácziné)/0000-0002-7637-7133; Minus, Annamária/0009-0003-4199-3942}
}

@article{MTMT:34405999,
	title = {GproteinDb in 2024: new G protein-GPCR couplings, AlphaFold2-multimer models and interface interactions},
	url = {https://m2.mtmt.hu/api/publication/34405999},
	author = {Pándy-Szekeres, Gáspár and Taracena Herrera, Luis P and Caroli, Jimmy and Kermani, Ali A and Kulkarni, Yashraj and Keserű, György Miklós and Gloriam, David E},
	doi = {10.1093/nar/gkad1089},
	journal-iso = {NUCLEIC ACIDS RES},
	journal = {NUCLEIC ACIDS RESEARCH},
	volume = {52},
	unique-id = {34405999},
	issn = {0305-1048},
	abstract = {G proteins are the major signal proteins of ∼800 receptors for medicines, hormones, neurotransmitters, tastants and odorants. GproteinDb offers integrated genomic, structural, and pharmacological data and tools for analysis, visualization and experiment design. Here, we present the first major update of GproteinDb greatly expanding its coupling data and structural templates, adding AlphaFold2 structure models of GPCR–G protein complexes and advancing the interactive analysis tools for their interfaces underlying coupling selectivity. We present insights on coupling agreement across datasets and parameters, including constitutive activity, agonist-induced activity and kinetics. GproteinDb is accessible at https://gproteindb.org.},
	year = {2024},
	eissn = {1362-4962},
	pages = {D466-D475},
	orcid-numbers = {Gloriam, David E/0000-0002-4299-7561}
}

@article{MTMT:35196297,
	title = {The PARP inhibitor rucaparib blocks SARS-CoV-2 virus binding to cells and the immune reaction in models of COVID-19},
	url = {https://m2.mtmt.hu/api/publication/35196297},
	author = {Papp, H. and Tóth, Emese and Bóvári-Biri, J. and Bánfai, K. and Juhász, P. and Mahdi, M. and Russo, L.C. and Bajusz, Dávid and Sipos, Adrienn and Petri, László and Szalai, Tibor Viktor and Kemény, Ágnes and Madai, M. and Kuczmog, A. and Batta, Gyula and Mózner, Orsolya and Vaskó, Dorottya and Hirsch, Edit and Bohus, P. and Méhes, G. and Tőzsér, J. and Curtin, N.J. and Helyes, Zsuzsanna and Tóth, A. and Hoch, N.C. and Jakab, F. and Keserű, György Miklós and Pongrácz, J.E. and Bay, Péter},
	doi = {10.1111/bph.17305},
	journal-iso = {BR J PHARMACOL},
	journal = {BRITISH JOURNAL OF PHARMACOLOGY},
	unique-id = {35196297},
	issn = {0007-1188},
	abstract = {Background and Purpose: To date, there are limited options for severe Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 virus. As ADP-ribosylation events are involved in regulating the life cycle of coronaviruses and the inflammatory reactions of the host; we have, here, assessed the repurposing of registered PARP inhibitors for the treatment of COVID-19. Experimental Approach: The effects of PARP inhibitors on virus uptake were assessed in cell-based experiments using multiple variants of SARS-CoV-2. The binding of rucaparib to spike protein was tested by molecular modelling and microcalorimetry. The anti-inflammatory properties of rucaparib were demonstrated in cell-based models upon challenging with recombinant spike protein or SARS-CoV-2 RNA vaccine. Key Results: We detected high levels of oxidative stress and strong PARylation in all cell types in the lungs of COVID-19 patients, both of which negatively correlated with lymphocytopaenia. Interestingly, rucaparib, unlike other tested PARP inhibitors, reduced the SARS-CoV-2 infection rate through binding to the conserved 493–498 amino acid region located in the spike-ACE2 interface in the spike protein and prevented viruses from binding to ACE2. In addition, the spike protein and viral RNA-induced overexpression of cytokines was down-regulated by the inhibition of PARP1 by rucaparib at pharmacologically relevant concentrations. Conclusion and Implications: These results point towards repurposing rucaparib for treating inflammatory responses in COVID-19. © 2024 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.},
	keywords = {NFκB; rucaparib; ACE2; COVID-19; SARS-CoV-2 spike protein; SARS-CoV-2 RNA; viral lung inflammation},
	year = {2024},
	eissn = {1476-5381},
	orcid-numbers = {Bajusz, Dávid/0000-0003-4277-9481; Kemény, Ágnes/0000-0002-4523-3938; Batta, Gyula/0000-0002-0442-1828; Mózner, Orsolya/0000-0001-5784-7702; Vaskó, Dorottya/0000-0002-2502-0644}
}

@article{MTMT:35134356,
	title = {Contribution of Noncovalent Recognition and Reactivity to the Optimization of Covalent Inhibitors : A Case Study on KRasG12C},
	url = {https://m2.mtmt.hu/api/publication/35134356},
	author = {Péczka, Nikolett and Randelovic, Ivan and Orgován, Zoltán and Csorba, Noémi and Egyed, Attila and Petri, László and Ábrányi-Balogh, Péter and Gadanecz, Márton and Perczel, András and Tóvári, József and Schlosser, Gitta (Vácziné) and Takács, Tamás and Mihalovits, Levente Márk and Ferenczy, György and Buday, László and Keserű, György Miklós},
	doi = {10.1021/acschembio.4c00217},
	journal-iso = {ACS CHEM BIOL},
	journal = {ACS CHEMICAL BIOLOGY},
	volume = {19},
	unique-id = {35134356},
	issn = {1554-8929},
	abstract = {Covalent drugs might bear electrophiles to chemically modify their targets and have the potential to target previously undruggable proteins with high potency. Covalent binding of drug-size molecules includes a noncovalent recognition provided by secondary interactions and a chemical reaction leading to covalent complex formation. Optimization of their covalent mechanism of action should involve both types of interactions. Noncovalent and covalent binding steps can be characterized by an equilibrium dissociation constant (KI) and a reaction rate constant (kinact), respectively, and they are affected by both the warhead and the scaffold of the ligand. The relative contribution of these two steps was investigated on a prototypic drug target KRASG12C, an oncogenic mutant of KRAS. We used a synthetically more accessible nonchiral core derived from ARS-1620 that was equipped with four different warheads and a previously described KRAS-specific basic side chain. Combining these structural changes, we have synthesized novel covalent KRASG12C inhibitors and tested their binding and biological effect on KRASG12C by various biophysical and biochemical assays. These data allowed us to dissect the effect of scaffold and warhead on the noncovalent and covalent binding event. Our results revealed that the atropisomeric core of ARS-1620 is not indispensable for KRASG12C inhibition, the basic side chain has little effect on either binding step, and warheads affect the covalent reactivity but not the noncovalent binding. This type of analysis helps identify structural determinants of efficient covalent inhibition and may find use in the design of covalent agents.},
	year = {2024},
	eissn = {1554-8937},
	pages = {1743-1756},
	orcid-numbers = {Randelovic, Ivan/0000-0003-0161-0022; Gadanecz, Márton/0009-0009-8076-7597; Perczel, András/0000-0003-1252-6416; Tóvári, József/0000-0002-5543-3204; Schlosser, Gitta (Vácziné)/0000-0002-7637-7133; Mihalovits, Levente Márk/0000-0003-1022-3294; Ferenczy, György/0000-0002-5771-4616; Buday, László/0000-0003-3518-5757}
}

@article{MTMT:35176724,
	title = {Site-Selective Antibody Conjugation with Dibromopyrazines.},
	url = {https://m2.mtmt.hu/api/publication/35176724},
	author = {Szepesi Kovács, Dénes and Pásztor, Bettina and Ábrányi-Balogh, Péter and Petri, László and Imre, Tímea and Simon, József and Tátrai, Enikő and Várady, György and Tóvári, József and Szijj, Peter A and Keserű, György Miklós},
	doi = {10.1021/acs.bioconjchem.4c00296},
	journal-iso = {BIOCONJUGATE CHEM},
	journal = {BIOCONJUGATE CHEMISTRY},
	volume = {Aug 16},
	unique-id = {35176724},
	issn = {1043-1802},
	abstract = {In recent years, antibody conjugates have evolved as state-of-the-art options for diagnostic and therapeutic applications. During site-selective antibody conjugation, incomplete rebridging of antibody chains limits the homogeneity of conjugates and calls for the development of new rebridging agents. Herein, we report a dibromopyrazine derivative optimized to reach highly homogeneous conjugates rapidly and with high conversion on rebridging of trastuzumab, even providing a feasible route for antibody modification in acidic conditions. Furthermore, coupling a fluorescent dye and a cytotoxic drug resulted in effective antibody conjugates with excellent serum stability and in vitro selectivity, demonstrating the utility of the dibromopyrazine rebridging agent to produce on-demand future antibody conjugates for diagnostic or therapeutic applications.},
	year = {2024},
	eissn = {1520-4812},
	orcid-numbers = {Tátrai, Enikő/0000-0001-9778-2077; Tóvári, József/0000-0002-5543-3204}
}

@article{MTMT:33845452,
	title = {SH2db, an information system for the SH2 domain},
	url = {https://m2.mtmt.hu/api/publication/33845452},
	author = {Bajusz, Dávid and Pándy-Szekeres, Gáspár and Takács, Ágnes and de Araujo, Elvin D and Keserű, György Miklós},
	doi = {10.1093/nar/gkad420},
	journal-iso = {NUCLEIC ACIDS RES},
	journal = {NUCLEIC ACIDS RESEARCH},
	volume = {51},
	unique-id = {33845452},
	issn = {0305-1048},
	abstract = {SH2 domains are key mediators of phosphotyrosine-based signalling, and therapeutic targets for diverse, mostly oncological, disease indications. They have a highly conserved structure with a central beta sheet that divides the binding surface of the protein into two main pockets, responsible for phosphotyrosine binding (pY pocket) and substrate specificity (pY + 3 pocket). In recent years, structural databases have proven to be invaluable resources for the drug discovery community, as they contain highly relevant and up-to-date information on important protein classes. Here, we present SH2db, a comprehensive structural database and webserver for SH2 domain structures. To organize these protein structures efficiently, we introduce (i) a generic residue numbering scheme to enhance the comparability of different SH2 domains, (ii) a structure-based multiple sequence alignment of all 120 human wild-type SH2 domain sequences and their PDB and AlphaFold structures. The aligned sequences and structures can be searched, browsed and downloaded from the online interface of SH2db (http://sh2db.ttk.hu), with functions to conveniently prepare multiple structures into a Pymol session, and to export simple charts on the contents of the database. Our hope is that SH2db can assist researchers in their day-to-day work by becoming a one-stop shop for SH2 domain related research.},
	year = {2023},
	eissn = {1362-4962},
	pages = {W542-W552},
	orcid-numbers = {Bajusz, Dávid/0000-0003-4277-9481}
}

@article{MTMT:34160949,
	title = {Covalent fragment approaches targeting non-cysteine residues},
	url = {https://m2.mtmt.hu/api/publication/34160949},
	author = {Csorba, Noémi and Ábrányi-Balogh, Péter and Keserű, György Miklós},
	doi = {10.1016/j.tips.2023.08.014},
	journal-iso = {TRENDS PHARMACOL SCI},
	journal = {TRENDS IN PHARMACOLOGICAL SCIENCES},
	volume = {44},
	unique-id = {34160949},
	issn = {0165-6147},
	year = {2023},
	eissn = {1873-3735},
	pages = {802-816}
}

@article{MTMT:33802561,
	title = {Allosteric regulation and crystallographic fragment screening of SARS-CoV-2 NSP15 endoribonuclease},
	url = {https://m2.mtmt.hu/api/publication/33802561},
	author = {Godoy, Andre Schutzer and Nakamura, Aline Minalli and Douangamath, Alice and Song, Yun and Noske, Gabriela Dias and Gawriljuk, Victor Oliveira and Fernandes, Rafaela Sachetto and Pereira, Humberto D Muniz and Oliveira, Ketllyn Irene Zagato and Fearon, Daren and Dias, Alexandre and Krojer, Tobias and Fairhead, Michael and Powell, Alisa and Dunnet, Louise and Brandao-Neto, Jose and Skyner, Rachael and Chalk, Rod and Bajusz, Dávid and Bege, Miklós and Borbás, Anikó and Keserű, György Miklós and von Delft, Frank and Oliva, Glaucius},
	doi = {10.1093/nar/gkad314},
	journal-iso = {NUCLEIC ACIDS RES},
	journal = {NUCLEIC ACIDS RESEARCH},
	volume = {51},
	unique-id = {33802561},
	issn = {0305-1048},
	abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). The NSP15 endoribonuclease enzyme, known as NendoU, is highly conserved and plays a critical role in the ability of the virus to evade the immune system. NendoU is a promising target for the development of new antiviral drugs. However, the complexity of the enzyme's structure and kinetics, along with the broad range of recognition sequences and lack of structural complexes, hampers the development of inhibitors. Here, we performed enzymatic characterization of NendoU in its monomeric and hexameric form, showing that hexamers are allosteric enzymes with a positive cooperative index, and with no influence of manganese on enzymatic activity. Through combining cryo-electron microscopy at different pHs, X-ray crystallography and biochemical and structural analysis, we showed that NendoU can shift between open and closed forms, which probably correspond to active and inactive states, respectively. We also explored the possibility of NendoU assembling into larger supramolecular structures and proposed a mechanism for allosteric regulation. In addition, we conducted a large fragment screening campaign against NendoU and identified several new allosteric sites that could be targeted for the development of new inhibitors. Overall, our findings provide insights into the complex structure and function of NendoU and offer new opportunities for the development of inhibitors.},
	year = {2023},
	eissn = {1362-4962},
	pages = {5255-5270},
	orcid-numbers = {Godoy, Andre Schutzer/0000-0002-0613-9164; Bajusz, Dávid/0000-0003-4277-9481; Borbás, Anikó/0000-0001-8462-4547; von Delft, Frank/0000-0003-0378-0017}
}

@article{MTMT:33647485,
	title = {Covalent fragment mapping of KRasG12C revealed novel chemotypes with in vivo potency},
	url = {https://m2.mtmt.hu/api/publication/33647485},
	author = {Orgován, Zoltán and Péczka, Nikolett and Petri, László and Ábrányi-Balogh, Péter and Randelovic, Ivan and Tóth, Szilárd and Szakács, Gergely and Nyíri, Kinga and Vértessy, Beáta (Grolmuszné) and Pálfy, Gyula and Vida, István and Perczel, András and Tóvári, József and Keserű, György Miklós},
	doi = {10.1016/j.ejmech.2023.115212},
	journal-iso = {EUR J MED CHEM},
	journal = {EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY},
	volume = {250},
	unique-id = {33647485},
	issn = {0223-5234},
	abstract = {G12C mutant KRas is considered druggable by allele-specific covalent inhibitors due to the nucleophilic character of the oncogenic mutant cysteine at position 12. Discovery of these inhibitors requires the optimization of both covalent and noncovalent interactions. Here, we report covalent fragment screening of our electrophilic fragment library of diverse non-covalent scaffolds equipped with 40 different electrophilic functionalities to identify fragments as suitable starting points targeting Cys12. Screening the library against KRasG12C using Ellman's free thiol assay, followed by protein NMR and cell viability assays, resulted in two potential inhibitor chemotypes. Characterization of these scaffolds in in vitro cellular- and in vivo xenograft models revealed them as promising starting points for covalent drug discovery programs.},
	year = {2023},
	eissn = {1768-3254},
	orcid-numbers = {Randelovic, Ivan/0000-0003-0161-0022; Pálfy, Gyula/0000-0003-1590-5331; Perczel, András/0000-0003-1252-6416; Tóvári, József/0000-0002-5543-3204}
}

@article{MTMT:33421768,
	title = {GPCRdb in 2023: state-specific structure models using AlphaFold2 and new ligand resources},
	url = {https://m2.mtmt.hu/api/publication/33421768},
	author = {Pándy-Szekeres, Gáspár and Caroli, Jimmy and Mamyrbekov, Alibek and Kermani, Ali A. and Keserű, György Miklós and Kooistra, Albert J. and Gloriam, David E.},
	doi = {10.1093/nar/gkac1013},
	journal-iso = {NUCLEIC ACIDS RES},
	journal = {NUCLEIC ACIDS RESEARCH},
	volume = {51},
	unique-id = {33421768},
	issn = {0305-1048},
	abstract = {G protein-coupled receptors (GPCRs) are physiologically abundant signaling hubs routing hundreds of extracellular signal substances and drugs into intracellular pathways. The GPCR database, GPCRdb supports > 5000 interdisciplinary researchers every month with reference data, analysis, visualization, experiment design and dissemination. Here, we present our fifth major GPCRdb release setting out with an overview of the many resources for receptor sequences, structures, and ligands. This includes recently published additions of class D generic residue numbers, a comparative structure analysis tool to identify functional determinants, trees clustering GPCR structures by 3D conformation, and mutations stabilizing inactive/active states. We provide new state-specific structure models of all human non-olfactory GPCRs built using AlphaFold2-MultiState. We also provide a new resource of endogenous ligands along with a larger number of surrogate ligands with bioactivity, vendor, and physiochemical descriptor data. The one-stop-shop ligand resources integrate ligands/data from the ChEMBL, Guide to Pharmacology, PDSP Ki and PubChem database. The GPCRdb is available athttps://gpcrdb.org.},
	year = {2023},
	eissn = {1362-4962},
	pages = {D395-D402}
}

@article{MTMT:33729477,
	title = {Activation-Free Sulfonyl Fluoride Probes for Fragment Screening},
	url = {https://m2.mtmt.hu/api/publication/33729477},
	author = {Petri, László and Ábrányi-Balogh, Péter and Csorba, Noémi and Keeley, Aaron Brian and Simon, József and Randelovic, Ivan and Tóvári, József and Schlosser, Gitta (Vácziné) and Szabó, Dániel and Drahos, László and Keserű, György Miklós},
	doi = {10.3390/molecules28073042},
	journal-iso = {MOLECULES},
	journal = {MOLECULES},
	volume = {28},
	unique-id = {33729477},
	issn = {1420-3049},
	abstract = {SuFEx chemistry is based on the unique reactivity of the sulfonyl fluoride group with a range of nucleophiles. Accordingly, sulfonyl fluorides label multiple nucleophilic amino acid residues, making these reagents popular in both chemical biology and medicinal chemistry applications. The reactivity of sulfonyl fluorides nominates this warhead chemotype as a candidate for an external, activation-free general labelling tag. Here, we report the synthesis and characterization of a small sulfonyl fluoride library that yielded the 3-carboxybenzenesulfonyl fluoride warhead for tagging tractable targets at nucleophilic residues. Based on these results, we propose that coupling diverse fragments to this warhead would result in a library of sulfonyl fluoride bits (SuFBits), available for screening against protein targets. SuFBits will label the target if it binds to the core fragment, which facilitates the identification of weak fragments by mass spectrometry.},
	keywords = {fragment screening; chemical probe; Electrophilic warhead; Sulfonyl fluoride; Targeted covalent inhibitor; covalent fragment},
	year = {2023},
	eissn = {1420-3049},
	orcid-numbers = {Randelovic, Ivan/0000-0003-0161-0022; Tóvári, József/0000-0002-5543-3204; Schlosser, Gitta (Vácziné)/0000-0002-7637-7133; Szabó, Dániel/0000-0003-3375-395X; Drahos, László/0000-0001-9589-6652}
}

@article{MTMT:34015800,
	title = {Synthesis and Application of Two-Photon Active Fluorescent Rhodol Dyes for Antibody Conjugation and In Vitro Cell Imaging},
	url = {https://m2.mtmt.hu/api/publication/34015800},
	author = {Szepesi Kovács, Dénes and Chiovini, Balázs and Müller, Dalma and Tóth, Estilla Zsófia and Fülöp, Anna and Ábrányi-Balogh, Péter and Wittner, Lucia and Várady, György and Farkas, Ödön and Turczel, Gábor and Katona, Gergely and Győrffy, Balázs and Keserű, György Miklós and Mucsi, Zoltán and Rózsa J., Balázs and Kovács, Ervin},
	doi = {10.1021/acsomega.3c01796},
	journal-iso = {ACS OMEGA},
	journal = {ACS OMEGA},
	volume = {8},
	unique-id = {34015800},
	issn = {2470-1343},
	year = {2023},
	eissn = {2470-1343},
	pages = {22836-22843},
	orcid-numbers = {Wittner, Lucia/0000-0001-6800-0953; Várady, György/0000-0003-2012-9680; Farkas, Ödön/0000-0002-4217-0150; Katona, Gergely/0000-0002-4173-0355; Győrffy, Balázs/0000-0002-5772-3766; Mucsi, Zoltán/0000-0003-3224-8847; Rózsa J., Balázs/0000-0003-1427-7003; Kovács, Ervin/0000-0002-3939-6925}
}

@article{MTMT:34205650,
	title = {Effective Synthesis, Development and Application of a Highly Fluorescent Cyanine Dye for Antibody Conjugation and Microscopy Imaging},
	url = {https://m2.mtmt.hu/api/publication/34205650},
	author = {Szepesi Kovács, Dénes and Kontra, Bence and Chiovini, Balázs and Müller, Dalma and Tóth, Estilla Zsófia and Ábrányi-Balogh, Péter and Wittner, Lucia and Várady, György and Turczel, Gábor and Farkas, Ödön and Owen, Michael Christopher and Katona, Gergely and Győrffy, Balázs and Keserű, György Miklós and Mucsi, Zoltán and Rózsa J., Balázs and Kovács, Ervin},
	doi = {10.1039/D3OB01471A},
	journal-iso = {ORG BIOMOL CHEM},
	journal = {ORGANIC & BIOMOLECULAR CHEMISTRY},
	volume = {21},
	unique-id = {34205650},
	issn = {1477-0520},
	abstract = {An asymmetric cyanine-type fluorescent dye was designed and synthesized via a versatile, multi-step process, aiming to conjugate with an Her2+ receptor specific antibody by an azide-alkyne click reaction. The aromaticity and the excitation and relaxation energetics of the fluorophore were characterized by computational methods. The synthesized dye exhibited excellent fluorescence properties for confocal microscopy, offering efficient applicability in in vitro imaging due to its merits such as a high molar absorption coefficient (36 816 M-1 cm-1), excellent brightness, optimal wavelength (627 nm), larger Stokes shift (26 nm) and appropriate photostability compared to cyanines. The conjugated cyanine-trastuzumab was constructed via an effective, metal-free, strain-promoted azide-alkyne click reaction leading to a regulated number of dyes being conjugated. This novel cyanine-labelled antibody was successfully applied for in vitro confocal imaging and flow cytometry of Her2+ tumor cells. An azido cyanine dye was synthesized and characterized by computational and experimental techniques and applied in tumor cell imaging.},
	keywords = {RECEPTOR; REAGENTS; FUTURE},
	year = {2023},
	eissn = {1477-0539},
	pages = {8829-8836},
	orcid-numbers = {Kontra, Bence/0000-0001-8293-3637; Wittner, Lucia/0000-0001-6800-0953; Várady, György/0000-0003-2012-9680; Farkas, Ödön/0000-0002-4217-0150; Katona, Gergely/0000-0002-4173-0355; Győrffy, Balázs/0000-0002-5772-3766; Mucsi, Zoltán/0000-0003-3224-8847; Rózsa J., Balázs/0000-0003-1427-7003; Kovács, Ervin/0000-0002-3939-6925}
}