Photoresponsive Control of G-Quadruplex DNA Systems

Abstract

G-quadruplex (G4) oligonucleotide secondary structures have recently attracted significant attention as therapeutic targets owing to their occurrence in human oncogene promoter sequences and the genome of pathogenic organisms. G4s also demonstrate interesting catalytic activities in their own right, as well as the ability to act as scaffolds for the development of DNA-based materials and nanodevices. Owing to this diverse range of opportunities to exploit G4 in a variety of applications, several strategies to control G4 structure and function have emerged. Interrogating the role of G4s in biology requires the delivery of small-molecule ligands that promote its formation under physiological conditions, while exploiting G4 in the development of responsive nanodevices is normally achieved by the addition and sequestration of the metal ions required for the stabilization of the folded structure. Although these strategies prove successful, neither allows the system in question to be controlled externally. Meanwhile, light has proven to be an attractive means for the control of DNA-based systems as it is noninvasive, can be delivered with high spatiotemporal precision, and is orthogonal to many chemical and biological processes. A plethora of photoresponsive DNA systems have been reported to date; however, the vast majority deploy photoreactive moieties to control the stability and assembly of duplex DNA hybrids. Despite the unique opportunities afforded by the regulation of G-quadruplex formation in biology, catalysis, and nanotechnology, comparatively little attention has been devoted to the design of photoresponsive G4-based systems. In this Perspective, we consider the potential of photoresponsive G4 assemblies and examine the strategies that may be used to engineer these systems toward a variety of applications. Through an overview of the main developments in the field to date, we highlight recent progress made toward this exciting goal and the emerging opportunities that remain ripe for further exploration in the coming years.

Stepping Out of the Blue: From Visible to Near‐IR Triggered Photoswitches

“…Photoswitches also offer many opportunities for polymer phase transition control [31,32] as well as power storage. [33,34] Beyond these applications, the recent boom in the development of biotechnology has also demonstrated photoswitches as valuable tools for the reversible activation/ deactivation of biomolecules [35,36] (e.g., peptides, [37] proteins, [38] oligonucleotides, [39] and metabolites [40] ). In these systems, light is as an ideal bio-orthogonal and remotecontrollable trigger that enables the spatiotemporal control of operations in specific tissue or even in single cells.…”

Feedback-controlled topological reconfiguration of molecular assemblies for programming supramolecular structures

“…The G-quartet is a macrocyclic structure which is stabilized by the formation of hydrogen bonds at the Hoogeteen face. [23][24][25][26][27][28][29][30][31][32] GMP has unique self-assembly behaviors under acidic conditions because of the formation of G-quartet and Gquadruplexes. 24,25,27,28 The phosphate groups of GMP endow the molecule with pH responsiveness and ion binding capacity.…”

Linear and Nonlinear Optical Properties of Azobenzene Derivatives Modified with an (Amino)naphthalene Moiety

“…The interest in development of molecular switches − arises from the fact that imparting external sensitivity to molecular systems is an efficient way to control on-demand their structure, properties, and functions and hence offers multiple applications in materials − and biological sciences. − Among various external triggers, light is the most desired kind of stimulus, because spatiotemporal resolution, excitation tunability, and biocompatibility are achieved through remote control. ,, A particularly important group of light-sensitive compounds in this context are azobenzenes (ABs) . The physicochemical and structural changes accompanying their E – Z photoisomerization, i.e., the photochromic effect, have been widely exploited to provide the strategy for material modification by means of light stimulation. , Up to now, azo compounds have been used to modulate the properties of supramolecular systems, − biomolecules (DNA, protein), , ion channels and receptors, , polymers, and liquid crystals, , in solution as well as on surfaces and bulk materials, transferring effects from the molecular level to the macroscopic scale .…”