RT Journal Article
T1 Stimuli-Responsive DNA Binding by Synthetic Systems
A1 Rodríguez Villar, Jéssica
A1 Mosquera Mosquera, Jesús
A1 Learte Aymamí, Soraya
A1 Vázquez Sentís, Marco Eugenio
A1 Mascareñas Cid, José Luis
K1 Peptides and proteins
K1 Ligands
K1 Genetics
K1 Nucleic acid structure
K1 Irradiation
AB Conspectus: DNA is the molecule responsible for the storage and transmission of the genetic information in living organisms. The expression of this information is highly regulated. In eukaryotes, it is achieved mainly at the transcription level thanks to specialized proteins called transcription factors (TFs) that recognize specific DNA sequences, thereby promoting or inhibiting the transcription of particular genes. In many cases, TFs are present in the cell in an inactive form but become active in response to an external signal, which might modify their localization and DNA binding properties or modulate their interactions with the rest of the transcriptional machinery. As a result of the crucial role of TFs, the design of synthetic peptides or miniproteins that can emulate their DNA binding properties and eventually respond to external stimuli is of obvious interest. On the other hand, although the B-form double helix is the most common DNA secondary structure, it is not the only one with an essential biological function. Guanine quadruplexes (GQs) have received considerable attention due to their critical role in the regulation of gene expression, which is usually associated with a change in the GQ conformation. Thus, the development of GQ probes whose properties can be controlled using external signals is also of significant relevance.In this Account, we present a summary of the recent efforts toward the development of stimuli-responsive synthetic DNA binders with a particular emphasis on our own contributions. We first introduce the structure of B and GQ DNAs, and some of the main factors underlying their selective recognition. We then discuss some of the different approaches used for the design of stimulus-mediated DNA binders. We have organized our discussion according to whether the interaction takes place with duplex or guanine quadruplex DNAs, and each section is divided according to the nature of the stimulus (i.e., physical or chemical). Regarding physical stimuli, light (through the incorporation of photolabile protecting groups or photoisomerizable agents) is the most common input for the activation/deactivation of DNA binding events. With respect to chemical signals, the use of metals (through the incorporation of metal-coordinating groups in the DNA binding agent) has allowed the development of a wide range of stimuli-responsive DNA binders. More recently, redox-based systems have also been used to control DNA interactions.This Account ends with a “Conclusions and Outlook” section highlighting some of the general lessons that have been learned and future directions toward further advancing the field
PB American Chemical Society
SN 0001-4842
YR 2020
FD 2020
LK http://hdl.handle.net/10347/23535
UL http://hdl.handle.net/10347/23535
LA eng
NO Acc. Chem. Res. 2020, 53, 10, 2286–2298
NO This document is the Accepted Manuscript version of a Published Work that appeared in final form in Accounts of chemical research, copyright © 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/acs.accounts.0c00415
NO Financial support from the Spanish Grants SAF2016-76689-R, RED2018-102417-T, RTI2018-099877-B-I00 the Xunta de Galicia (2015-CP082, ED431B 2018/04, ED431C-2017/19 and Centro Singular de Investigación de Galicia accreditation 2019-2022, ED431G 2019/03), the European Union (European Regional Development Fund - ERDF), and the European Research Council (Advanced Grant No. 340055) are gratefully acknowledged
DS Minerva
RD 30 abr 2026