Photocaged and Mixed Photocaged Bioreversible‐Protected ATP Derivatives as Tools for the Controlled Release of ATP

Abstract

Adenosine triphosphate (ATP) is known as the universal energy source for cellular processes, in addition, ATP also plays an important role in inflammation and cell signaling. Extracellular ATP binds to purinergic receptors and initiates further immune responses. To investigate these processes in‐depth and to understand the complex mechanism of purinergic signaling, chemical tools are necessary. Here we present the synthesis of different photocaged ATP derivatives and the investigation of the light‐induced release of ATP depending on the different synthesized photocleavable protecting groups based on the 2‐nitrobenzyl moiety. Furthermore, we also present the synthesis of a mixed protected ATP‐derivative as an example for a novel class of lipophilically caged nucleoside triphosphates. This new type of compounds is protected with a highly lipophilic non‐toxic bio‐removable acyloxybenzyl group and a photocleavable group. This combination may allow both passive cell uptake and controlled release of ATP by irradiation with non‐harmful UV light.

ATP/azobenzene-guanidinium self-assembly into fluorescent and multi-stimuli-responsive supramolecular aggregates

“…Besides enzymes and metal ions, light constitutes a highly desired trigger to control self-assemblies due to its precise spatiotemporal control, tunability (wavelength, power) and remote character 26 . Light-responsive ATP-based systems to photochemically control the release of this nucleotide have been described but this involved photocleavable bonds, therefore precluding any photo-reversible response 27 . To our knowledge, photoreversible supramolecular assemblies involving unmodified ATP have yet to be demonstrated.…”

ATP/azobenzene-guanidinium self-assembly into fluorescent and multi-stimuli responsive supramolecular aggregates

“…Besides enzymes and metals, light constitutes a highly desired trigger to control self-assemblies due to its precise spatiotemporal control, tunability (wavelength, power) and remote character 25 . Light-responsive ATP-based systems to photochemically control the release of this nucleotide have been described but this involved photocleavable bounds, therefore precluding any photo-reversible response 26 . To our knowledge, photoreversible supramolecular assemblies involving unmodified ATP have yet to be demonstrated.…”

Intracellular delivery and deep tissue penetration of nucleoside triphosphates using photocleavable covalently bound dendritic polycations

“…To avoid anabolic bottlenecks, also NMP, NDP, and more recently NTP prodrugs have been introduced. 3,4,[9][10][11][12][13] Common prodrug approaches can result in limited uptake efficiency into tissues, as the phosphate masking groups are designed to be quickly removed in cells, which hampers deep tissue penetration. Likewise, clinically used aryl amidate prodrugs, such as sofosbuvir, tenofovir alafenamide, and remdesivir are also based on enzymatic hydrolysis, in which the activation of the prodrugs are not potentially subject to an extracellular trigger.…”