RT Journal Article T1 Streamlined Identification of Metallopeptides for Intracellular Catalysis Using Positionally Addressable Combinatorial Libraries A1 González González, Carmen A1 Martínez Castro, Laura A1 Learte Aymamí, Soraya A1 Pose Insua, Clara A1 Couceiro, José R. A1 Martin-Malpartida, Pau A1 Macias, Maria J. A1 Maréchal, Jean-Didier A1 Mascareñas Cid, José Luis A1 Vázquez Sentís, Marco Eugenio K1 Catalysis K1 Peptides K1 Combinatorial chemistry K1 Computational chemistry K1 Biocatalysis AB The discovery and development of artificial catalysts to carry out bioorthogonal reactions in living cells is a primary goal at the interface of Chemistry and Biology. Current approaches rely on time-consuming trial-and-error methods. As an alternative, we show that positionally addressable combinatorial libraries (SPOT libraries) provide a significant advantage for the efficient identification of novel catalytic metallopeptides. Using these libraries, we were able to rapidly identify catalytic β-hairpin palladopeptides capable of promoting efficient depropargylation reactions in challenging intracellular environments. PB American Chemical Society YR 2025 FD 2025-05-08 LK https://hdl.handle.net/10347/41855 UL https://hdl.handle.net/10347/41855 LA eng NO ACS Catal. 2025, 15, 10, 8624–8632 NO This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Catalysis, copyright © 2025 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acscatal.5c00525 NO We gratefully acknowledge grants RTI2018-099877-B-I00, PID2021- 122909NB-I00, and PID2021-127702NB-I00 funded by MCIN/AEI/10.13039/501100011033 and by ERDF A way of making Europe. This work has received financial support from the Xunta de Galicia (ED431C 2021/29, 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 SGR1323 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. DS Minerva RD 24 abr 2026