TY  - CONF
AU  - Moros, Alejandro José Mahía
AU  - Engsted Kiib, Anders
AU  - Nišavić, Marija
AU  - Palmfeldt, Johan
AU  - Poulsen, Thomas
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12948
UR  - https://pure.au.dk/portal/en/publications/a-stable-%CE%B1-lactam-as-electrophilic-warhead-for-bioconjugation-and-2
AB  - Electrophilic warheads are one of the key pillars upon which chemical biology is founded, constituting the anchor point for the design of targeted covalent inhibitors, the identification of novel therapeutic targets, and the development of a wide diversity of bioconjugation and proteomic profiling techniques.[1] Within the panorama of continuous expansion of chemical biology applications, a great interest has grown in the discovery of new biologically relevant electrophilic warheads that contribute to broaden the current scope of action. That is the case of 3-membered N-heterocyclic compounds, whose electronic properties and structural strain trigger their potential as chemical tools in biological research.[2,3] However, up to date, there aren´t known utilities within this field for a potentially relevant member of the aforementioned family: the α-lactams. Here we show how an α-lactam reagent can be efficiently employed in the framework of bioconjugation and proteomic profiling. We have designed and synthesised a stable α-lactam (AM2) compatible with aqueous buffers and studied the reaction outcome and kinetics with benzylamine and benzyl mercaptane under different conditions. Higher reactivity was detected with the latter. We have further demonstrated that AM2 is attached to free cysteine residues in peptides, potentially as a thioester. Additionally, liver carboxylesterase 1 (CES1), with key roles in both endo- and xenobiotic metabolism,[4] was found as a selective target for AM2 in HepG2 cells and cell lysate. All in all, we anticipate AM2 to be a starting point for the development of new and more sophisticated α-lactam-based electrophilic probes for their use in covalent chemical biology.
C3  - 22nd Tetrahedron Symposium
T1  - A stable α-lactam as electrophilic warhead for bioconjugation and proteomic profiling
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12948
ER  - 

@conference{
author = "Moros, Alejandro José Mahía and Engsted Kiib, Anders and Nišavić, Marija and Palmfeldt, Johan and Poulsen, Thomas",
year = "2022",
abstract = "Electrophilic warheads are one of the key pillars upon which chemical biology is founded, constituting the anchor point for the design of targeted covalent inhibitors, the identification of novel therapeutic targets, and the development of a wide diversity of bioconjugation and proteomic profiling techniques.[1] Within the panorama of continuous expansion of chemical biology applications, a great interest has grown in the discovery of new biologically relevant electrophilic warheads that contribute to broaden the current scope of action. That is the case of 3-membered N-heterocyclic compounds, whose electronic properties and structural strain trigger their potential as chemical tools in biological research.[2,3] However, up to date, there aren´t known utilities within this field for a potentially relevant member of the aforementioned family: the α-lactams. Here we show how an α-lactam reagent can be efficiently employed in the framework of bioconjugation and proteomic profiling. We have designed and synthesised a stable α-lactam (AM2) compatible with aqueous buffers and studied the reaction outcome and kinetics with benzylamine and benzyl mercaptane under different conditions. Higher reactivity was detected with the latter. We have further demonstrated that AM2 is attached to free cysteine residues in peptides, potentially as a thioester. Additionally, liver carboxylesterase 1 (CES1), with key roles in both endo- and xenobiotic metabolism,[4] was found as a selective target for AM2 in HepG2 cells and cell lysate. All in all, we anticipate AM2 to be a starting point for the development of new and more sophisticated α-lactam-based electrophilic probes for their use in covalent chemical biology.",
journal = "22nd Tetrahedron Symposium",
title = "A stable α-lactam as electrophilic warhead for bioconjugation and proteomic profiling",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12948"
}

Moros, A. J. M., Engsted Kiib, A., Nišavić, M., Palmfeldt, J.,& Poulsen, T.. (2022). A stable α-lactam as electrophilic warhead for bioconjugation and proteomic profiling. in 22nd Tetrahedron Symposium.
https://hdl.handle.net/21.15107/rcub_vinar_12948

Moros AJM, Engsted Kiib A, Nišavić M, Palmfeldt J, Poulsen T. A stable α-lactam as electrophilic warhead for bioconjugation and proteomic profiling. in 22nd Tetrahedron Symposium. 2022;.
https://hdl.handle.net/21.15107/rcub_vinar_12948 .

Moros, Alejandro José Mahía, Engsted Kiib, Anders, Nišavić, Marija, Palmfeldt, Johan, Poulsen, Thomas, "A stable α-lactam as electrophilic warhead for bioconjugation and proteomic profiling" in 22nd Tetrahedron Symposium (2022),
https://hdl.handle.net/21.15107/rcub_vinar_12948 .

TY  - CONF
AU  - Moros, Alejandro José Mahía
AU  - Kiib, Anders Engsted
AU  - Nišavić, Marija
AU  - Palmfeldt, Johan
AU  - Poulsen, Thomas
PY  - 2022
UR  - https://pure.au.dk/portal/en/publications/studies-on-the-applicability-of-a-stable-alpha-lactam-as-electrop
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12949
C3  - The Danish Chemical Society Annual Meeting 2022
T1  - Studies on the applicability of a stable alpha-lactam as electrophilic probe for bioconjugation and proteomic profiling
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12949
ER  - 

@conference{
author = "Moros, Alejandro José Mahía and Kiib, Anders Engsted and Nišavić, Marija and Palmfeldt, Johan and Poulsen, Thomas",
year = "2022",
journal = "The Danish Chemical Society Annual Meeting 2022",
title = "Studies on the applicability of a stable alpha-lactam as electrophilic probe for bioconjugation and proteomic profiling",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12949"
}

Moros, A. J. M., Kiib, A. E., Nišavić, M., Palmfeldt, J.,& Poulsen, T.. (2022). Studies on the applicability of a stable alpha-lactam as electrophilic probe for bioconjugation and proteomic profiling. in The Danish Chemical Society Annual Meeting 2022.
https://hdl.handle.net/21.15107/rcub_vinar_12949

Moros AJM, Kiib AE, Nišavić M, Palmfeldt J, Poulsen T. Studies on the applicability of a stable alpha-lactam as electrophilic probe for bioconjugation and proteomic profiling. in The Danish Chemical Society Annual Meeting 2022. 2022;.
https://hdl.handle.net/21.15107/rcub_vinar_12949 .

Moros, Alejandro José Mahía, Kiib, Anders Engsted, Nišavić, Marija, Palmfeldt, Johan, Poulsen, Thomas, "Studies on the applicability of a stable alpha-lactam as electrophilic probe for bioconjugation and proteomic profiling" in The Danish Chemical Society Annual Meeting 2022 (2022),
https://hdl.handle.net/21.15107/rcub_vinar_12949 .