RT Journal Article T1 Metal-Dependent DNA Recognition and Cell Internalization of Designed, Basic Peptides A1 Learte Aymamí, Soraya A1 Curado, Natalia A1 Rodríguez Villar, Jéssica A1 Vázquez Sentís, Marco Eugenio A1 Mascareñas Cid, José Luis AB A fragment of the DNA basic region (br) of the GCN4 bZIP transcription factor has been modified to include two His residues at designed i and i+4 positions of its N-terminus. The resulting monomeric peptide (brHis2) does not bind to its consensus target DNA site (5′-GTCAT-3′). However, addition of Pd(en)Cl2 (en, ethylenediamine) promotes a high-affinity interaction with exquisite selectivity for this sequence. The peptide–DNA complex is disassembled by addition of a slight excess of a palladium chelator, and the interaction can be reversibly switched multiple times by playing with controlled amounts of either the metal complex or the chelator. Importantly, while the peptide brHis2 fails to translocate across cell membranes on its own, addition of the palladium reagent induces an efficient cell internalization of this peptide. In short, we report (1) a designed, short peptide that displays highly selective, major groove DNA binding, (2) a reversible, metal-dependent DNA interaction, and (3) a metal-promoted cell internalization of this basic peptide PB American Chemical Society SN 0002-7863 YR 2017 FD 2017 LK http://hdl.handle.net/10347/18335 UL http://hdl.handle.net/10347/18335 LA eng NO Learte-Aymamí, S., Curado, N., Rodríguez, J., Vázquez, M., & Mascareñas, J. (2017). Metal-Dependent DNA Recognition and Cell Internalization of Designed, Basic Peptides. Journal Of The American Chemical Society, 139(45), 16188-16193. doi: 10.1021/jacs.7b07422 NO This work has received financial support from the MINECO (SAF2013-41943-R, SAF2016-76689-R, and CTQ2015-70698-R), the Xunta de Galicia (2015-CP082, ED431C 2017/19, and Centro Singular de Investigación de Galicia Accreditation 2016–2019, ED431G/09), the European Union (European Regional Development Fund, ERDF), and the European Research Council (Advanced Grant No. 340055). Support of COST CM1306 and the orfeo-cinqa network are also acknowledged. J.R. thanks the Xunta de Galicia for a Ph.D. fellowship. We also wish to acknowledge the generous support by the Fundación AECC (IDEAS197VAZQ grant) DS Minerva RD 27 abr 2026