Light-mediated in cell downregulation of G-quadruplex-containing genes using a photo-caged ligand

Murat, Pierre; Gormally, Michael V.; Sanders, Debbie; Antonio, Marco Di; Balasubramanian, Shankar

doi:10.1039/c3cc44737e

Cited by 31 publications

(30 citation statements)

References 25 publications

(18 reference statements)

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“…Furthermore, a small number of responsive G4 ligands have also been described. In these cases, the activity of the ligand is unlocked in response to a stimulus, such as photoirradiation or the redox environment . Such approaches allow an additional level of spatiotemporal control over the system, and therefore potential to act as starting points for a new generation of smart drugs where activity can be controlled with greater precision to minimize off‐target side effects , .…”

Section: Introductionmentioning

confidence: 99%

Binding and Beyond: What Else Can G‐Quadruplex Ligands Do?

2019

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G‐quadruplexes (G4) are four‐stranded structures formed from guanine‐rich oligonucleotides. Their defined 3D structures and polymorphic nature set them apart from classical nucleic acid morphology and suggest a range of potential applications in the development of functional materials. Meanwhile, the occurrence of G4 across the genomes of animals, plants and pathogens suggests roles for these structures in biology that may be exploited for therapeutic effect. Hundreds of G4 ligands are reported to bind these sequences with high specificity and affinity, but such ligands can also be engineered to do more than simply associate with G4 in a straightforward host‐guest fashion. Ligands have been developed that can switch G4 topology, direct the selective covalent modification of nucleic acid structures, or respond to external stimuli to permit spatiotemporal control of their activity. Herein we survey the main themes of such “value‐added” G4 ligands and consider the opportunities and challenges of their potential applications.

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Section: Introductionmentioning

confidence: 99%

Binding and Beyond: What Else Can G‐Quadruplex Ligands Do?

2019

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“…These peptide segments were adapted from the peptide model sequence CRANK-OH 18 . In our case, we substituted the arginine for the unnatural amino acid Dap(PhCn), which bears a photolabile lipid group 44,45 at the N β position of 2,3-diaminopropionic acid (Dap). The photolabile group possesses a linear aliphatic alkyl chain of either C8 (2a) or C16 (2b).…”

Section: Resultsmentioning

confidence: 99%

“…Photoliberation of the lipid-free peptides. Without purification, the nitrobenzyl photocaging group was removed using a standard photocleavage protocol 45 , liberating the lipid-free peptide. This photochemical process allowed the generation of the uncaged peptide product 4 in nearly quantitative yield (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…When the native chemical ligation was completed, the reaction mixture containing the product LYRMGCDap(PhC16)ANK (3b) was directly transferred to a quartz tube. Then, the solution was irradiated with UV light (365 nm) for 5 min 45 . Afterwards, an aliquot was taken and analyzed by analytical HPLC-MS and the formation of the peptide 4 was observed.…”

Section: Synthesis Of Lyrmgcdapank (4)mentioning

confidence: 99%

“…Our approach takes advantage of a peptide bearing a C-terminal alkyl thioester (1a-d, 5a,b or 6a,b), which is capable of forming micelles in aqueous solution. Addition of an Cys-peptide containing a photolabile lipid 44,45 moiety near the Nterminus (2a,b) leads to rapid NCL. We hypothesize that the close proximity [46][47][48][49][50] of the alkyl thioester and cysteine within formed micelles increases the rate of transthioesterification substantially, even at low concentrations of reagents (1 mM as standard concentration) and in the absence of thiol catalysts.…”

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confidence: 99%

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Traceless native chemical ligation of lipid-modified peptide surfactants by mixed micelle formation

et al. 2020

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Biology utilizes multiple strategies, including sequestration in lipid vesicles, to raise the rate and specificity of chemical reactions through increases in effective molarity of reactants. We show that micelle-assisted reaction can facilitate native chemical ligations (NCLs) between a peptide-thioesterin which the thioester leaving group contains a lipid-like alkyl chainand a Cys-peptide modified by a lipid-like moiety. Hydrophobic lipid modification of each peptide segment promotes the formation of mixed micelles, bringing the reacting peptides into close proximity and increasing the reaction rate. The approach enables the rapid synthesis of polypeptides using low concentrations of reactants without the need for thiol catalysts. After NCL, the lipid moiety is removed to yield an unmodified ligation product. This micelle-based methodology facilitates the generation of natural peptides, like Magainin 2, and the derivatization of the protein Ubiquitin. Formation of mixed micelles from lipid-modified reactants shows promise for accelerating chemical reactions in a traceless manner.

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Metal‐free Deoxygenative 2‐Amidation of Quinoline N‐oxides with Nitriles via a Radical Activation Pathway

et al. 2018

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A metal-, base-and reductant-free approach for the efficient synthesis of various Nacylated 2-aminoquinolines was reported. In this work, readily available nitriles are used as the amide source, and methyl carbazate as both the radical activating reagent and oxygen source. This is the first report on the ester-radical-activated highly regioselective addition of nitriles to quinolone N-oxides. This procedure is expected to complement the current methods for functionalization of N-oxides via an electrophilic activation mechanism.

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Light-mediated in cell downregulation of G-quadruplex-containing genes using a photo-caged ligand

Abstract: The use of a caged G-quadruplex ligand allows for transcriptional control of quadruplex-containing genes using UV light as an external trigger.

Cited by 31 publications

References 25 publications

Binding and Beyond: What Else Can G‐Quadruplex Ligands Do?

Binding and Beyond: What Else Can G‐Quadruplex Ligands Do?

Traceless native chemical ligation of lipid-modified peptide surfactants by mixed micelle formation

Metal‐free Deoxygenative 2‐Amidation of Quinoline N‐oxides with Nitriles via a Radical Activation Pathway

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