RT Journal Article
T1 De Novo Engineering of Pd-Metalloproteins and Their Use as Intracellular Catalysts
A1 Learte Aymamí, Soraya
A1 Martínez Castro, Laura
A1 González González, Carmen
A1 Condeminas Rodríguez, Miriam
A1 Martín Malpartida, Pau
A1 Tomás Gamasa, María
A1 Baúlde Álvarez, Sandra
A1 Couceiro, José R.
A1 Maréchal, Jean-Didier
A1 Macias, Maria J.
A1 Mascareñas Cid, José Luis
A1 Vázquez Sentís, Marco Eugenio
K1 Intracellular catalysis
K1 Peptide engineering
K1 Metallopeptides
K1 Grafting
K1 Palladium
K1 Organometallic catalysis
AB The development of transition metal-based catalytic platforms that promote bioorthogonal reactions inside living cells remains a major challenge in chemical biology. This is particularly true for palladium-based catalysts, which are very powerful in organic synthesis but perform poorly in the cellular environment, mainly due to their rapid deactivation. We now demonstrate that grafting Pd(II) complexes into engineered β-sheets of a model WW domain results in cell-compatible palladominiproteins that effectively catalyze depropargylation reactions inside HeLa cells. The concave shape of the WW domain β-sheet proved particularly suitable for accommodating the metal center and protecting it from rapid deactivation in the cellular environment. A thorough NMR and computational study confirmed the formation of the metal-stapled peptides and allowed us to propose a three-dimensional structure for this novel metalloprotein motif
PB ACS
SN 2691-3704
YR 2024
FD 2024-06-23
LK http://hdl.handle.net/10347/34877
UL http://hdl.handle.net/10347/34877
LA eng
NO JACS Au 2024, 4, 7, 2630–2639
NO We thank grants RYC2020-029150-I and “ESF Investing in your future”, RTI2018-099877-B-I00, PID2019-108624RB-I00, PID2021-127702NB-I00, PID2021-122909NB-I00, and PID2022-137318OB-I00 funded by MCIN/AEI/10.13039/501100011033 and by ERDF A way of making Europe. We also thank MCIN/ISCIII and the “European Union Next Generation EU/PRTR” (GrantIHRC22 00009), and the ORFEO-CINQA network (RED2022-134287-T). This work has received financial support from the Xunta de Galicia (Centro de investigación do Sistema universitario de Galicia accreditation 2023–2027, ED431G 2023/03) and the European Union (European Regional Development Fund - ERDF). J.-D.M. and M.J.M. acknowledge the support of Agency for Management of University and Research Grants AGAUR, (2017 SGR-1323 and 2021 SGR-866). M.J.M. acknowledges the BBVA Foundation and institutional funding from IRB Barcelona, the CERCA Programme of the Catalan Government, and the MICINN through the Centers of Excellence Severo Ochoa award. M.J.M. is an ICREA Programme Investigator. M.C. acknowledges financial support from the Spanish Ministry of Education through the National Program FPU (FPU20/03153). M.T.-G. acknowledges financial support RYC2020-029150-I, from the Spanish Government
DS Minerva
RD 29 abr 2026