TY - JOUR AU - Kozma, Eszter AU - Kele, Péter TI - Bioorthogonal Reactions in Bioimaging JF - TOPICS IN CURRENT CHEMISTRY J2 - TOP CURR CHEM (2016-) VL - 382 PY - 2024 IS - 1 PG - 31 SN - 2365-0869 DO - 10.1007/s41061-024-00452-1 UR - https://m2.mtmt.hu/api/publication/34684024 ID - 34684024 AB - Visualization of biomolecules in their native environment or imaging-aided understanding of more complex biomolecular processes are one of the focus areas of chemical biology research, which requires selective, often site-specific labeling of targets. This challenging task is effectively addressed by bioorthogonal chemistry tools in combination with advanced synthetic biology methods. Today, the smart combination of the elements of the bioorthogonal toolbox allows selective installation of multiple markers to selected targets, enabling multicolor or multimodal imaging of biomolecules. Furthermore, recent developments in bioorthogonally applicable probe design that meet the growing demands of superresolution microscopy enable more complex questions to be addressed. These novel, advanced probes enable highly sensitive, low-background, single- or multiphoton imaging of biological species and events in live organisms at resolutions comparable to the size of the biomolecule of interest. Herein, the latest developments in bioorthogonal fluorescent probe design and labeling schemes will be discussed in the context of in cellulo/in vivo (multicolor and/or superresolved) imaging schemes. The second part focuses on the importance of genetically engineered minimal bioorthogonal tags, with a particular interest in site-specific protein tagging applications to answer biological questions. LA - English DB - MTMT ER - TY - PAT AU - Bojtár, Márton Gáspár AU - EGYED, ALEXANDRA AU - NÉMETH, KRISZTINA AU - Kele, Péter TI - VISIBLE LIGHT SENSITIVE PHOTOREMOVABLE PROTECTING GROUPS, PREPARATION PROCESS THEREOF, PHOTOACTIVATABLE CONJUGATES COMPRISING THEM AND USES THEREOF PY - 2024 UR - https://m2.mtmt.hu/api/publication/34773104 ID - 34773104 LA - English DB - MTMT ER - TY - PAT AU - Reményi, Attila AU - Soós, Tibor AU - Póti, Ádám Levente AU - Bálint, Dániel AU - Alexa, Anita AU - Sok, Péter Dániel AU - Torda, Lili AU - Varga, Szilárd AU - Ozsváth, Kristóf AU - Albert, Krisztián AU - Palkó, Roberta AU - Ember, Orsolya AU - Kállainé Szarka, Eszter AU - Imre, Timea TI - Cyclic designer scaffolds for the covalent targeting of proteins via michael addition PY - 2024 UR - https://m2.mtmt.hu/api/publication/35161458 ID - 35161458 AB - Many biologically active natural products contain electrophilic Michael acceptor fragments. For example, curcumin and 4-hydroxyderricin contain an acyclic α,β-unsaturated ketone that alkylates cysteines. Other antitumor or anti-inflammatory herbal compounds such as Withaferin A or zerumbone contain cyclic α,β-unsaturated ketones and react with nucleophilic residues of proteins. These observations contributed to a paradigm shift in drug design and development in the last two decades: various drugs with covalent warhead have been developed and approved. Despite the apparent importance and success of covalent warheads in current drug design and developments, the applied warheads display a rather limited structural variance and complexity which automatically limits the attainable chemical space. Furthermore, to minimize possible side-reactions during the synthesis of drugs, the applied warheads are added appendages in the late-stage of the synthetic route, thus a warhead scaffold that can be synthetically easily varied using orthogonal chemistry and used as a tunable covalent warhead is still missing. Such a structurally more complex scaffold would be much more like the warheads of the natural products and is expected to be more selective in targeting nucleophiles found on the proteins. Moreover, owing to a larger contact surface, it might be more suitable for targeting shallow protein surfaces involved in protein-protein interactions. LA - English DB - MTMT ER - TY - JOUR AU - Bálint, Dániel AU - Póti, Ádám Levente AU - Alexa, Anita AU - Sok, Péter Dániel AU - Albert, Krisztián AU - Torda, Lili AU - Földesi-Nagy, Dóra AU - Csókás, Dániel AU - Turczel, Gábor AU - Imre, Timea AU - Kállainé Szarka, Eszter AU - Fekete, Ferenc AU - Bento, Isabel AU - Bojtár, Márton Gáspár AU - Palkó, Roberta AU - Szabó, Pál Tamás AU - Monostory, Katalin AU - Pápai, Imre AU - Soós, Tibor AU - Reményi, Attila TI - Reversible covalent c-Jun N-terminal kinase inhibitors targeting a specific cysteine by precision-guided Michael-acceptor warheads JF - NATURE COMMUNICATIONS J2 - NAT COMMUN VL - 15 PY - 2024 IS - 1 PG - 19 SN - 2041-1723 DO - 10.1038/s41467-024-52573-2 UR - https://m2.mtmt.hu/api/publication/35435905 ID - 35435905 LA - English DB - MTMT ER - TY - JOUR AU - Kele, Péter TI - Nobel-díj klikkelésért? JF - MAGYAR KÉMIKUSOK LAPJA J2 - MAGY KEM LAP VL - 78 PY - 2023 IS - 2 SP - 34 EP - 36 PG - 3 SN - 0025-0163 UR - https://m2.mtmt.hu/api/publication/33609031 ID - 33609031 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Egyed, Alexandra AU - Németh, Krisztina AU - Molnár , Tibor Ákos AU - Kállay, Mihály AU - Kele, Péter AU - Bojtár, Márton Gáspár TI - Turning Red without Feeling Embarrassed─Xanthenium-Based Photocages for Red-Light-Activated Phototherapeutics JF - JOURNAL OF THE AMERICAN CHEMICAL SOCIETY J2 - J AM CHEM SOC VL - 145 PY - 2023 IS - 7 SP - 4026 EP - 4034 PG - 9 SN - 0002-7863 DO - 10.1021/jacs.2c11499 UR - https://m2.mtmt.hu/api/publication/33650038 ID - 33650038 N1 - Chemical Biology Research Group, Institute of Organic Chemistry, Research Centre for Natural Sciences, Magyar tudósok krt. 2., Hungary Hevesy György PhD School of Chemistry, Eötvös Loránd University, Pázmány Péter sétány 1/a., Hungary Department of Physical Chemistry and Materials Science, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Müegyetem rkp. 3., Hungary ELKH-BME Quantum Chemistry Research Group, Müegyetem rkp. 3., Hungary MTA-BME Lendület Quantum Chemistry Research Group, Müegyetem rkp. 3., Hungary CODEN: JACSA Correspondence Address: Kele, P.; Chemical Biology Research Group, Magyar tudósok krt. 2., Hungary; email: kele.peter@ttk.hu Correspondence Address: Bojtár, M.; Chemical Biology Research Group, Magyar tudósok krt. 2., Hungary; email: bojtar.marton@ttk.hu LA - English DB - MTMT ER - TY - JOUR AU - Németh, Krisztina AU - László, Zsófia AU - Biró, Adrienn AU - Szatmári, Ágnes AU - Cserép, Balázs Gergely AU - Várady, György AU - Bakos, Éva AU - Laczka, Csilla AU - Kele, Péter TI - Organic anion transporting polypeptide 3A1 (OATP3A1)-gated bioorthogonal labeling of intracellular proteins JF - MOLECULES J2 - MOLECULES VL - 28 PY - 2023 IS - 6 PG - 10 SN - 1431-5157 DO - 10.3390/molecules28062521 UR - https://m2.mtmt.hu/api/publication/33688209 ID - 33688209 N1 - Chemical Biology Research Group, Institute of Organic Chemistry, RCNS, Magyar Tudósok Krt. 2, Budapest, H-1117, Hungary Molecular Cell Biology Research Group, Institute of Enzymology, RCNS, Magyar Tudósok Krt. 2, Budapest, H-1117, Hungary Membrane Protein Research Group, Institute of Enzymology, RCNS, Magyar Tudósok Krt. 2, Budapest, H-1117, Hungary Export Date: 19 April 2023 CODEN: MOLEF Correspondence Address: Németh, K.; Chemical Biology Research Group, Magyar Tudósok Krt. 2, Hungary; email: nemeth.krisztina@ttk.hu Correspondence Address: Kele, P.; Chemical Biology Research Group, Magyar Tudósok Krt. 2, Hungary; email: kele.peter@ttk.hu Chemicals/CAS: protein, 67254-75-5; Fluorescent Dyes; Organic Anion Transporters; Proteins Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH, NKFIH-K-138518, NKFIH-K-143581, VEKOP-2.3.3-15-2016-00011 Funding text 1: Present work was supported by the National Research, Development and Innovation Office of Hungary (NKFIH-K-143581, NKFIH-K-138518 and VEKOP-2.3.3-15-2016-00011). AB - Organic anion transporting polypeptides (OATPs) were found to readily deliver membrane impermeable, tetrazine bearing fluorescent probes into cells. This feature was explored in OATP3A1 conditioned bio-orthogonal labeling schemes of various intracellular proteins in live cells. Confocal microscopy and super-resolution microscopy (STED) studies have shown that highly specific and efficient staining of the selected intracellular proteins can be achieved with the otherwise non-permeable probes when OATP3A1 is present in the cell membrane of cells. Such a transport protein linked bio-orthogonal labeling scheme is believed to be useful in OATP3A1 activity-controlled protein expression studies in the future. © 2023 by the authors. LA - English DB - MTMT ER - TY - JOUR AU - Kozma, Eszter AU - Bojtár, Márton Gáspár AU - Kele, Péter TI - Bioorthogonally assisted phototherapy: recent advances and prospects JF - ANGEWANDTE CHEMIE-INTERNATIONAL EDITION J2 - ANGEW CHEM INT EDIT VL - 62 PY - 2023 IS - 33 PG - 11 SN - 1433-7851 DO - 10.1002/anie.202303198 UR - https://m2.mtmt.hu/api/publication/33854599 ID - 33854599 AB - Photoresponsive materials offer excellent spatiotemporal control over biological processes and the emerging phototherapeutic methods are expected to have significant effects on targeted cancer therapies. Recent examples show that combination of photoactivatable approaches with bioorthogonal chemistry enhances the precision of targeted phototherapies and profound implications are foreseen particularly in the treatment of disperse/diffuse tumors. The extra level of on‐target selectivity and improved spatial/temporal control considerably intensified related bioorthogonally assisted phototherapy research. The anticipated growth of further developments in the field justifies the timeliness of a brief summary of the state of the art. LA - English DB - MTMT ER - TY - JOUR AU - Albitz, Evelin AU - Nemeth, Krisztina AU - Knorr, Gergely AU - Kele, Péter TI - Evaluation of bioorthogonally applicable tetrazine-Cy3 probes for fluorogenic labeling schemes JF - ORGANIC & BIOMOLECULAR CHEMISTRY J2 - ORG BIOMOL CHEM VL - 21 PY - 2023 IS - 36 SP - 7358 EP - 7366 PG - 9 SN - 1477-0520 DO - 10.1039/d3ob01204b UR - https://m2.mtmt.hu/api/publication/34310530 ID - 34310530 AB - The fluorogenic features of three sets of tetrazine-Cy3 probes were evaluated in bioorthogonal tetrazine-cyclooctyne ligation schemes. These studies revealed that the more efficient, internal conversion-based quenching of fluorescence by the tetrazine modul is translated to improved fluorogenicity compared to the more conventional, energy transfer-enabled design. Furthermore, a comparison of directly conjugated probes and vinylene-linked tetrazine-Cy3 probes revealed that more intimate conjugation of the tetrazine and the chromophore results in more efficient IC-based quenching even in spectral ranges where tetrazine exhibits diminished modulation efficiency. The applicability of these tetrazine-quenched fluorogenic Cy3 probes was demonstrated in the fluorogenic labeling schemes of the extra- and intracellular proteins of live cells.Evaluation of tetrazine-modulated fluorogenic Cy3 probes revealed that internal conversion-based quenching of fluorescence results in better fluorogenic performances even in spectral ranges where tetrazines have diminished modulation power. LA - English DB - MTMT ER - TY - JOUR AU - Albitz, Evelin AU - Kern, Dóra AU - Kormos, Attila AU - Bojtár, Márton Gáspár AU - Török, György AU - Biró, Adrienn AU - Szatmári, Ágnes AU - Németh, Krisztina AU - Kele, Péter TI - Bioorthogonal Ligation-Activated Fluorogenic FRET Dyads JF - ANGEWANDTE CHEMIE-INTERNATIONAL EDITION J2 - ANGEW CHEM INT EDIT VL - 61 PY - 2022 IS - 6 PG - 7 SN - 1433-7851 DO - 10.1002/anie.202111855 UR - https://m2.mtmt.hu/api/publication/32552957 ID - 32552957 N1 - Funding Agency and Grant Number: Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund [NKFIH-K-131439, NKFIH-FK-137589, NKFIH-PD-135121]; New National Excellence Program of the Ministry for Innovation and Technology [UNKP-21-3]; Eotvos Lorand Research Network [KEP-6] Funding text: This work has been implemented with the support provided by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, financed under the NKFIH-K-131439, NKFIH-FK-137589 and NKFIH-PD-135121 funding Schemes. We are also grateful for the generous support of Eotvos Lorand Research Network (KEP-6, FIKU). DK is grateful for the support of the uNKP-21-3 (New National Excellence Program of the Ministry for Innovation and Technology). AB - An energy transfer‐based signal amplification relay concept enabling transmission of bioorthogonally activatable fluorogenicity of blue‐excitable coumarins to yellow/red emitting cyanine frames is presented. Such relay mechanism resulted in improved cyanine fluorogenicities together with increased photostabilities and large apparent Stokes‐shifts allowing lower background fluorescence even in no‐wash bioorthogonal fluorogenic labeling schemes of intracellular structures in live cells. These energy transfer dyads sharing the same donor moiety together with their parent donor molecule allowed three‐color imaging of intracellular targets using one single excitation source with separate emission windows. Sub‐diffraction imaging of intracellular structures using the bioorthogonally activatable FRET dyads by STED microscopy is also presented. LA - English DB - MTMT ER -