# Gold-promoted arylation of biomolecules: selenocysteine chemoselective modification by cyclometallated gold(III) compounds

Ioannis Kanavos, Douglas Hideki Nakahata, Raphael Enoque Ferraz de Paiva, Luisa Ronga

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Ioannis Kanavos, Douglas Hideki Nakahata, Raphael Enoque Ferraz de Paiva, Luisa Ronga. Gold-promoted arylation of biomolecules: selenocysteine chemoselective modification by cyclometallated gold(III) compounds. BioNEXT: AEBIN young Researchers Symposium, Mar 2024, San Sebastian, Spain. hal-04524762

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Submitted on 28 Mar 2024

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# Gold-promoted arylation of biomolecules: selenocysteine chemoselective modification by cyclometallated gold(III) compounds

I. Kanavos,<fnref n="1" /> D. H. Nakahata,<fnref n="2" /> R. Lobinski,<fnref n="1" /> R. E. F. de Paiva<fnref n="2" /> and L. Ronga<fnref n="1" />

A low pKa (5.2), high polarizable volume (3.8 Å), and proneness to oxidation under ambient conditions make selenocysteine (Sec, U) a unique, natural reactive handle present in most organisms across all domains of life<fnref n="1" />. Sec modification offers a unique and unexplored potential for site-selective modification and probing of proteins.

Our investigation is focused on the use of cyclometallated gold(III) compounds for the chemoselective arylation of selenobiomolecules<fnref n="2" />. Here, the ability of several organometallic gold(III) compounds to promote the C-Se coupling in the active sites of Glutathion Peroxidase and Thiroedoxin Reductase was studied by liquid chromatography coupled to electrospray tandem mass spectrometry. The conditions enabling the selective arylation of Se over S were found in selenoproteins, containing both Sec and Cys. Moreover, in competitive experiments, selenopeptides are preferentially arylated by gold(III) compounds, even in the presence of large excess of their Cys counterparts.

<figure><img src="image_1.png" /><figcaption>Figure 1. Selective arylation of Sec in GPx1 demonstrated by LC-ESI MS/MS</figcaption></figure>

## References:

1. R. Mousa, R. N. Dardashti, N. Metanis, Angew Chem Int Ed. **2017**, *56*, 15818–15827, DOI: **10.1002/anie.201706876**.

2. D. H. Nakahata, I. Kanavos, M. Zubiria-Ulacia, A. Inague, L. Salassa, R. Lobinski, S. Miyamoto, J. M. Matxain, L. Ronga, R. E. F. de Paiva, *Chem. - Eur. J.* **2023**, in press, DOI: **10.1002/chem.202304050**.

<footnote n="1">¹ Institut des Sciences Analytiques et de Physico-Chimie Pour l'Environnement et les Matériaux - IPREM, Université de Pau et des Pays de l'Adour, E2S UPPA, CNRS, i.kanavos@univ-pau.fr</footnote>

<footnote n="2">² Donostia International Physics Center - DIPC, Paseo Manuel de Lardizabal 4, 20018 Donostia, Euskadi, Gipuzkoa, Spain</footnote>
# Gold-promoted arylation of biomolecules: selenocysteine chemoselective modification by cyclometallated gold(III) compounds

I. Kanavos,<fnref n="1" /> D. H. Nakahata,<fnref n="2" /> R. Lobinski,<fnref n="1" /> R. E. F. de Paiva<fnref n="2" /> and L. Ronga<fnref n="1" />

A low pKa (5.2), high polarizable volume (3.8 Å), and proneness to oxidation under ambient conditions make selenocysteine (Sec, U) a unique, natural reactive handle present in most organisms across all domains of life<fnref n="1" />. Sec modification offers a unique and unexplored potential for site-selective modification and probing of proteins.

Our investigation is focused on the use of cyclometallated gold(III) compounds for the chemoselective arylation of selenobiomolecules<fnref n="2" />. Here, the ability of several organometallic gold(III) compounds to promote the C-Se coupling in the active sites of Glutathion Peroxidase and Thiroedoxin Reductase was studied by liquid chromatography coupled to electrospray tandem mass spectrometry. The conditions enabling the selective arylation of Se over S were found in selenoproteins, containing both Sec and Cys. Moreover, in competitive experiments, selenopeptides are preferentially arylated by gold(III) compounds, even in the presence of large excess of their Cys counterparts.

<figure><img src="image_2.png" /><figcaption>Figure 1. Selective arylation of Sec in GPx1 demonstrated by LC-ESI MS/MS</figcaption></figure>

## References:

1. R. Mousa, R. N. Dardashti, N. Metanis, Angew Chem Int Ed. **2017**, *56*, 15818–15827, DOI: **10.1002/anie.201706876**.

2. D. H. Nakahata, I. Kanavos, M. Zubiria-Ulacia, A. Inague, L. Salassa, R. Lobinski, S. Miyamoto, J. M. Matxain, L. Ronga, R. E. F. de Paiva, *Chem. - Eur. J.* **2023**, in press, DOI: **10.1002/chem.202304050**.

<footnote n="1">¹ Institut des Sciences Analytiques et de Physico-Chimie Pour l'Environnement et les Matériaux - IPREM, Université de Pau et des Pays de l'Adour, E2S UPPA, CNRS, i.kanavos@univ-pau.fr</footnote>

<footnote n="2">² Donostia International Physics Center – DIPC, Paseo Manuel de Lardizabal 4, 20018 Donostia, Euskadi, Gipuzkoa, Spain</footnote>
**Acknowledgements:** This research has received funding from the European Union's Horizon 2020 Research and Innovation under the Marie Skłodowska-Curie Grant Agreement N° 945416 through the PhD fellowship of IK. This project has also received funding from "la Caixa" Foundation (ID 100010434) through the Junior Leader fellowship to RdP (LCF/BQ/PI22/11910033).
**Acknowledgements:** This research has received funding from the European Union's Horizon 2020 Research and Innovation under the Marie Skłodowska-Curie Grant Agreement N° 945416 through the PhD fellowship of IK. This project has also received funding from "la Caixa" Foundation (ID 100010434) through the Junior Leader fellowship to RdP (LCF/BQ/PI22/11910033).