Use of a Coumarin-Labeled Hexa-Arginine Peptide as a Fluorescent Hydroxyl Radical Probe in a Nanoparticulate Plasmid DNA Condensate

Perry, Christopher C.; Tang, Vicky J.; Konigsfeld, Katie; Aguilera, Joseph; Milligan, Jamie R.

doi:10.1021/jp205198b

Cited by 20 publications

(23 citation statements)

References 47 publications

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“…Optical imaging of biomarkers is an active area of study with several investigators exploring the use of C3CA labels for radiometric assessment [ 23 , 24 , 25 ]. The present investigation explored C3CA in gelatin as a potential RFG dosimeter.…”

Section: Introductionmentioning

confidence: 99%

Radio-Fluorogenic Gel Dosimetry with Coumarin

et al. 2018

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Gel dosimeters are attractive detectors for radiation therapy, with properties similar to biological tissue and the potential to visualize volumetric dose distributions. Radio-fluorogenesis is the yield of fluorescent chemical products in response to energy deposition from ionizing radiation. This report shares the development of a novel radio-fluorogenic gel (RFG) dosimeter, gelatin infused with coumarin-3-carboxlyic acid (C3CA), for the quantification of imparted energy. Aqueous solutions exposed to ionizing radiation result in the production of hydroxyl free radicals through water radiolysis. Interactions between hydroxyl free radicals and coumarin-3-carboxylic acid produce a fluorescent product. 7-hydroxy-coumarin-3-carboxylic acid has a blue (445 nm) emission following ultra-violet (UV) to near UV (365–405 nm) excitation. Effects of C3CA concentration and pH buffers were investigated. The response of the RFG was explored with respect to strength, type, and exposure rate of high-energy radiation. Results show a linear dose response relationship independent of energy and type, with a dose-rate dependency. This report demonstrates increased photo-yield with high pH and the utility of gelatin-RFG for phantom studies of radiation dosimetry.

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Section: Introductionmentioning

confidence: 99%

Radio-Fluorogenic Gel Dosimetry with Coumarin

et al. 2018

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“…Optical imaging of biomarkers is an active area of study with C3CA a recognized radiation activated sensor for fluorescent imaging [18]. Investigators have explored the use of coumarin attached to peptide ligands, designed for DNA binding, with potential for assessment of radiological response [23]. Other work is currently studying the application of fluorescent labels for radiometric assay [24,25].…”

Section: Discussionmentioning

confidence: 99%

Gel Dosimetry with Radio-Fluorogenic Coumarin

Sandwall¹,

Bastow²,

Spitz³

et al. 2018

Preprint

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Abstract:In radiotherapy, accurate deposition of energy to the targeted volume is vital to ensure 9 effective treatment. Gel dosimeters are attractive detection systems, as tissue substitutes with 10 potential to yield three-dimensional dose distributions. Radio-fluorogenesis is creation fluorescent 11 chemical products in response to energy deposition from high-energy radiation. This report shares 12 studies of a radio-fluorogenic gel dosimetry system, gelatin with coumarin-3-carboxlyic acid 13 (C3CA), for the quantification of imparted energy. Aqueous solutions exposed to ionizing radiation 14 result in the production of hydroxyl free radicals through water radiolysis. Interactions between 15 hydroxyl free radicals and coumarin-3-carboxylic acid produce a fluorescent product.

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“…The experimental DNA target has 8 base pairs (charge Z = −8 + −8 = −16) bound by 2× Ac-BPA-Arg 6 -NH 2 and 1× Ac-Arg 4 -NH 2 ligands (Z = 6 + 6 + 4 = +16) (see Discussion). From the strand break yield in plasmid DNA condensed with a hexa-arginine ligand (Perry et al, 2011), the hydroxyl radical diffusion distance is ca. 5 nm.…”

Section: Modeling Of Energy Deposition By Neutronsmentioning

confidence: 99%

“…To mitigate this undesirable effect, we made use of the combination of a limiting concentration of a boron-containing ligand having a larger binding constant and an excess of a boron-free ligand with a smaller binding constant. We have described a related approach in the case of a fluorescent hydroxyl radical probe (Perry et al, 2011).…”

Section: Ligand Structurementioning

confidence: 99%

DNA condensation with a boron-containing cationic peptide for modeling boron neutron capture therapy

Perry

Ramos-Méndez

Milligan

2020

Radiation Physics and Chemistry

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The amino acid derivative 4-borono-L-phenylalanine (BPA) has been used in the radiation medicine technique boron neutron capture therapy (BNCT). Here we have characterized its interaction with DNA when incorporated into a positively charged hexa-L-arginine peptide. This ligand binds strongly to DNA and induces its condensation, an effect which is attenuated at higher ionic strengths. The use of an additional tetra-L-arginine ligand enables the preparation of a DNA condensate in the presence of a negligible concentration of unbound boron. Under these conditions, Monte Carlo simulation indicates that >85% of energy deposition events resulting from thermal neutron irradiation derive from boron fission. The combination of experimental model systems and simulations that we describe here provides a valuable tool for accurate track structure modeling of the DNA damage produced by the high LET particles involved in BNCT.

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Use of a Coumarin-Labeled Hexa-Arginine Peptide as a Fluorescent Hydroxyl Radical Probe in a Nanoparticulate Plasmid DNA Condensate

Cited by 20 publications

References 47 publications

Radio-Fluorogenic Gel Dosimetry with Coumarin

Radio-Fluorogenic Gel Dosimetry with Coumarin

Gel Dosimetry with Radio-Fluorogenic Coumarin

DNA condensation with a boron-containing cationic peptide for modeling boron neutron capture therapy

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