@article{MTMT:35435914,
	title = {Targeting a key protein-protein interaction surface on mitogen-activated protein kinases by a precision-guided warhead scaffold},
	url = {https://m2.mtmt.hu/api/publication/35435914},
	author = {Póti, Ádám Levente and Bálint, Dániel and Alexa, Anita and Sok, Péter Dániel and Ozsváth, Kristóf and Albert, Krisztián and Turczel, Gábor and Magyari, Sarolt and Ember, Orsolya and Papp, Kinga and Király, Sándor Balázs and Imre, Timea and Németh, Krisztina and Kurtán, Tibor and Gógl, Gergő and Varga, Szilárd and Soós, Tibor and Reményi, Attila},
	doi = {10.1038/s41467-024-52574-1},
	journal-iso = {NAT COMMUN},
	journal = {NATURE COMMUNICATIONS},
	volume = {15},
	unique-id = {35435914},
	issn = {2041-1723},
	abstract = {For mitogen-activated protein kinases (MAPKs) a shallow surface—distinct from the substrate binding pocket—called the D(ocking)-groove governs partner protein binding. Screening of broad range of Michael acceptor compounds identified a double-activated, sterically crowded cyclohexenone moiety as a promising scaffold. We show that compounds bearing this structurally complex chiral warhead are able to target the conserved MAPK D-groove cysteine via reversible covalent modification and interfere with the proteinprotein interactions of MAPKs. The electronic and steric properties of the Michael acceptor can be tailored via different substitution patterns. The inversion of the chiral center of the warhead can reroute chemical bond formation with the targeted cysteine towards the neighboring, but less nucleophilic histidine. Compounds bind to the shallow MAPK D-groove with low micromolar affinity in vitro and perturb MAPK signaling networks in the cell. This class of chiral, cyclic and enhanced 3D shaped Michael acceptor scaffolds offers an alternative to conventional ATP-competitive drugs modulating MAPK signaling pathways.},
	year = {2024},
	eissn = {2041-1723},
	orcid-numbers = {Albert, Krisztián/0009-0004-0516-604X; Magyari, Sarolt/0000-0003-4573-0915; Varga, Szilárd/0000-0001-9611-5168}
}

@article{MTMT:35435905,
	title = {Reversible covalent c-Jun N-terminal kinase inhibitors targeting a specific cysteine by precision-guided Michael-acceptor warheads},
	url = {https://m2.mtmt.hu/api/publication/35435905},
	author = {Bálint, Dániel and Póti, Ádám Levente and Alexa, Anita and Sok, Péter Dániel and Albert, Krisztián and Torda, Lili and Földesi-Nagy, Dóra and Csókás, Dániel and Turczel, Gábor and Imre, Timea and Kállainé Szarka, Eszter and Fekete, Ferenc and Bento, Isabel and Bojtár, Márton Gáspár and Palkó, Roberta and Szabó, Pál Tamás and Monostory, Katalin and Pápai, Imre and Soós, Tibor and Reményi, Attila},
	doi = {10.1038/s41467-024-52573-2},
	journal-iso = {NAT COMMUN},
	journal = {NATURE COMMUNICATIONS},
	volume = {15},
	unique-id = {35435905},
	issn = {2041-1723},
	year = {2024},
	eissn = {2041-1723},
	orcid-numbers = {Albert, Krisztián/0009-0004-0516-604X; Bojtár, Márton Gáspár/0000-0001-8459-4659; Szabó, Pál Tamás/0000-0003-2260-4641}
}

@{MTMT:35161458,
	title = {Cyclic designer scaffolds for the covalent targeting of proteins via michael addition},
	url = {https://m2.mtmt.hu/api/publication/35161458},
	author = {Reményi, Attila and Soós, Tibor and Póti, Ádám Levente and Bálint, Dániel and Alexa, Anita and Sok, Péter Dániel and Torda, Lili and Varga, Szilárd and Ozsváth, Kristóf and Albert, Krisztián and Palkó, Roberta and Ember, Orsolya and Kállainé Szarka, Eszter and Imre, Timea},
	unique-id = {35161458},
	abstract = {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.},
	year = {2024},
	orcid-numbers = {Varga, Szilárd/0000-0001-9611-5168}
}