Interference with DNA repair after ionizing radiation by a pyrrole-imidazole polyamide

Diaz-Perez, Silvia; Kane, Nathanael; Kurmis, Alexis A.; Yang, Fei; Kummer, Nicolas; Dervan, Peter B.; Nickols, Nicholas G.

doi:10.1371/journal.pone.0196803

Cited by 4 publications

(3 citation statements)

References 31 publications

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“…Interestingly, the structural alteration caused by these minor groove-binding synthetic cyclic PIPs disrupted the binding of major groove-binding transcription factors such as the androgen and glucocorticoid receptors ( 96 ). This allosteric perturbation of the DNA helix provides a molecular basis for disruption of transcription factor−DNA interfaces by small molecules and may be applied to the chemical control of gene networks ( 97–100 ).…”

Section: Ligand-induced Structures Of the Dna Duplexmentioning

confidence: 99%

A survey of recent unusual high-resolution DNA structures provoked by mismatches, repeats and ligand binding

Satange

Chang

Hou

2018

Nucleic Acids Research

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The structure of the DNA duplex is arguably one of the most important biological structures elucidated in modern history. DNA duplex structure is closely associated with essential biological functions such as DNA replication and RNA transcription. In addition to the classical A-, B- and Z-DNA conformations, DNA duplexes are capable of assuming a variety of alternative conformations depending on the sequence and environmental context. A considerable number of these unusual DNA duplex structures have been identified in the past decade, and some of them have been found to be closely associated with different biological functions and pathological conditions. In this manuscript, we review a selection of unusual DNA duplex structures, particularly those originating from base pair mismatch, repetitive sequence motifs and ligand-induced structures. Although the biological significance of these novel structures has not yet been established in most cases, the illustrated conformational versatility of DNA could have relevance for pharmaceutical or nanotechnology development. A perspective on the future directions of this field is also presented.

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Section: Ligand-induced Structures Of the Dna Duplexmentioning

confidence: 99%

A survey of recent unusual high-resolution DNA structures provoked by mismatches, repeats and ligand binding

Satange

Chang

Hou

2018

Nucleic Acids Research

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“…ImP significantly blunted the increase of NF-κB after irradiation. It has been reported that the pre-treatment of glioma cells with a pyrrole-imidazole (Py-Im) polyamide prior to exposure to ionizing radiation resulted in a delay in the resolution of phosphorylated γ-H2AX foci that are indicative of the delayed repair of double-stranded breaks [ 45 ]. However, ImP, the classic downstream metabolite of l -Histidine, activated different signaling pathways to perform radioprotective functions in radiation-induced lung injury.…”

Section: Discussionmentioning

confidence: 99%

Gut Microbiota-Derived l-Histidine/Imidazole Propionate Axis Fights against the Radiation-Induced Cardiopulmonary Injury

Chen

Wang

Dong

et al. 2021

IJMS

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Radiation-induced cardiopulmonary injuries are the most common and intractable side effects that are entwined with radiotherapy for thorax cancers. However, the therapeutic options for such complications have yielded disappointing results in clinical applications. Here, we reported that gut microbiota-derived l-Histidine and its secondary metabolite imidazole propionate (ImP) fought against radiation-induced cardiopulmonary injury in an entiric flora-dependent manner in mouse models. Local chest irradiation decreased the level of l-Histidine in fecal pellets, which was increased following fecal microbiota transplantation. l-Histidine replenishment via an oral route retarded the pathological process of lung and heart tissues and improved lung respiratory and heart systolic function following radiation exposure. l-Histidine preserved the gut bacterial taxonomic proportions shifted by total chest irradiation but failed to perform radioprotection in gut microbiota-deleted mice. ImP, the downstream metabolite of l-Histidine, accumulated in peripheral blood and lung tissues following l-Histidine replenishment and protected against radiation-induced lung and heart toxicity. Orally gavaged ImP could not enter into the circulatory system in mice through an antibiotic cocktail treatment. Importantly, ImP inhibited pyroptosis to nudge lung cell proliferation after radiation challenge. Together, our findings pave a novel method of protection against cardiopulmonary complications intertwined with radiotherapy in pre-clinical settings and underpin the idea that gut microbiota-produced l-Histidine and ImP are promising radioprotective agents.

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“…Diaz‐Perez et al. (2018) 109 explored the potential of PIPs as sensitizers to genotoxic therapies. Pre‐treatment of cells with a PIP before exposure to ionizing radiation delayed the resolution of phosphorylated γ‐H2AX foci, increased XRCC1 foci, and reduced cellular replication potential.…”

Section: Designing Pips To Modulate Diverse Transcriptional Targetsmentioning

confidence: 99%

Nucleic acid‐based small molecules as targeted transcription therapeutics for immunoregulation

Bai,

Ziadlou,

Vaijayanthi

et al. 2023

Allergy

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Transcription therapy is an emerging approach that centers on identifying the factors associated with the malfunctioning gene transcription machinery that causes diseases and controlling them with designer agents. Until now, the primary research focus in therapeutic gene modulation has been on small‐molecule drugs that target epigenetic enzymes and critical signaling pathways. However, nucleic acid‐based small molecules have gained popularity in recent years for their amenability to be pre‐designed and realize operative control over the dynamic transcription machinery that governs how the immune system responds to diseases. Pyrrole–imidazole polyamides (PIPs) are well‐established DNA‐based small‐molecule gene regulators that overcome the limitations of their conventional counterparts owing to their sequence‐targeted specificity, versatile regulatory efficiency, and biocompatibility. Here, we emphasize the rational design of PIPs, their functional mechanisms, and their potential as targeted transcription therapeutics for disease treatment by regulating the immune response. Furthermore, we also discuss the challenges and foresight of this approach in personalized immunotherapy in precision medicine.

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Interference with DNA repair after ionizing radiation by a pyrrole-imidazole polyamide

Cited by 4 publications

References 31 publications

A survey of recent unusual high-resolution DNA structures provoked by mismatches, repeats and ligand binding

A survey of recent unusual high-resolution DNA structures provoked by mismatches, repeats and ligand binding

Gut Microbiota-Derived l-Histidine/Imidazole Propionate Axis Fights against the Radiation-Induced Cardiopulmonary Injury

Nucleic acid‐based small molecules as targeted transcription therapeutics for immunoregulation

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