Role of Distance in Singlet Oxygen Applications: A Model System

Klaper, Matthias; Fudickar, Werner; Linker, Torsten

doi:10.1021/jacs.6b01555

Cited by 45 publications

(33 citation statements)

References 53 publications

(40 reference statements)

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“…Porphyrins could oxidize proteins with relative selectivity because of their ability to bind proteins in their native conformation, forming a sensitizer-acceptor complex 16 . Similar systems, where the oxidant source was coupled to its target, have also been reported 126, 127. Due to the noncovalent nature of the binding, porphyrin-protein complexes disaggregate when porphyrin is extracted 16 .…”

Section: Mechanism Of Porphyrin-induced Protein Aggregationmentioning

confidence: 70%

“…In step 1, PP-IX binds to proteins in their native states, independent of light, 16 leading to localized unfolding and conformational changes 144, 145. Porphyrin binding to target proteins helps circumvent the extreme labile nature of the ROS, namely 1 O 2 (intracellular diffusion distance of 10–20 nm and a lifetime of 10–40 ns before it is quenched) 113, 127, 146. Photosensitized 1 O 2 generation (see inset) by protein-bound porphyrins causes selective oxidation (step 2) and subsequently porphyrin-protein aggregates are formed through noncovalent interactions between oxidized proteins-porphyrins and porphyrin-porphyrin(s), (step 3).…”

Section: Mechanism Of Porphyrin-induced Protein Aggregationmentioning

confidence: 99%

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Porphyrin-Induced Protein Oxidation and Aggregation as a Mechanism of Porphyria-Associated Cell Injury

Maitra

Cunha

Elenbaas

et al. 2019

Cellular and Molecular Gastroenterology and Hepatology

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Porphyrias are caused by pathological accumulation of porphyrins and their precursors, with liver damage and cancer risk, photosensitivity, and neurovisceral involvement. Fluorescent porphyrins bind proteins reversibly and lead, in the presence of oxygen, to protein oxidation and aggregation with consequent cellular damage. Genetic porphyrias comprise eight diseases caused by defects in the heme biosynthetic pathway that lead to accumulation of heme precursors. Consequences of porphyria include photosensitivity, liver damage and increased risk of hepatocellular carcinoma, and neurovisceral involvement, including seizures. Fluorescent porphyrins that include protoporphyrin-IX, uroporphyrin and coproporphyrin, are photo-reactive; they absorb light energy and are excited to high-energy singlet and triplet states. Decay of the porphyrin excited to ground state releases energy and generates singlet oxygen. Porphyrin-induced oxidative stress is thought to be the major mechanism of porphyrin-mediated tissue damage. Although this explains the acute photosensitivity in most porphyrias, lightinduced porphyrin-mediated oxidative stress does not account for the effect of porphyrins on internal organs. Recent findings demonstrate the unique role of fluorescent porphyrins in causing subcellular compartment-selective protein aggregation. Porphyrin-mediated protein aggregation associates with nuclear deformation, cytoplasmic vacuole formation and endoplasmic reticulum dilation. Porphyrin-triggered proteotoxicity is compounded by inhibition of the proteasome due to aggregation of some of its subunits. The ensuing disruption in proteostasis also manifests in cell cycle arrest coupled with aggregation of cell proliferation-related proteins, including PCNA, cdk4 and cyclin B1. Porphyrins bind to native proteins and, in presence of light and oxygen, oxidize several amino acids, particularly methionine. Noncovalent interaction of oxidized proteins with porphyrins leads to formation of protein aggregates. In internal organs, particularly the liver, light-independent porphyrin-mediated protein aggregation occurs after secondary triggers of oxidative stress. Thus, porphyrin-induced protein aggregation provides a novel mechanism for external and internal tissue damage in porphyrias that involve fluorescent porphyrin accumulation.

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Section: Mechanism Of Porphyrin-induced Protein Aggregationmentioning

confidence: 70%

Section: Mechanism Of Porphyrin-induced Protein Aggregationmentioning

confidence: 99%

Porphyrin-Induced Protein Oxidation and Aggregation as a Mechanism of Porphyria-Associated Cell Injury

Maitra

Cunha

Elenbaas

et al. 2019

Cellular and Molecular Gastroenterology and Hepatology

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“…9 The explanation that is normally given is that the PS needs to bind strongly to the negatively charged Gram-negative outer membrane, because singlet oxygen has such a short diffusion distance. 10 This strong binding between bacteria and PS can best be achieved with PS that have a pronounced cationic charge, but not with neutral/anionic PS such as Photofrin (PF). 11 Moreover, there is evidence 12 that cationic PS can also penetrate into the Gram-negative cells by the “self-promoted uptake pathway”.…”

mentioning

confidence: 99%

Potassium Iodide Potentiates Broad-Spectrum Antimicrobial Photodynamic Inactivation Using Photofrin

et al. 2017

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It is known that noncationic porphyrins such as Photofrin (PF) are effective in mediating antimicrobial photodynamic inactivation (aPDI) of Gram-positive bacteria or fungi. However, the aPDI activity of PF against Gram-negative bacteria is accepted to be extremely low. Here we report that the nontoxic inorganic salt potassium iodide (KI) at a concentration of 100 mM when added to microbial cells (108/mL) + PF (10 μM hematoporphyrin equivalent) + 415 nm light (10 J/cm2) can eradicate (>6 log killing) five different Gram-negative species (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, and Acinetobacter baumannii), whereas no killing was obtained without KI. The mechanism of action appears to be the generation of microbicidal molecular iodine (I2/I3−) as shown by comparable bacterial killing when cells were added to the mixture after completion of illumination and light-dependent generation of iodine as detected by the formation of the starch complex. Gram-positive methicillin-resistant Staphylococcus aureus is much more sensitive to aPDI (200–500 nM PF), and in this case potentiation by KI may be mediated mainly by short-lived iodine reactive species. The fungal yeast Candida albicans displayed intermediate sensitivity to PF-aPDI, and killing was also potentiated by KI. The reaction mechanism occurs via singlet oxygen (1O2). KI quenched 1O2 luminescence (1270 nm) at a rate constant of 9.2 × 105 M−1 s−1. Oxygen consumption was increased when PF was illuminated in the presence of KI. Hydrogen peroxide but not superoxide was generated from illuminated PF in the presence of KI. Sodium azide completely inhibited the killing of E. coli with PF/blue light + KI.

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“…2,3 This is the underlying first step in photodynamic therapy (PDT) 4 -which has attracted considerable experimental and theoretical attention. [5][6][7][8] PDT is a form of medicinal treatment in which light induces the photosensitised formation of cellular 1 O 2 . The nascent 1 O 2 has been shown to induce cell death -efficiently killing microbial cells.…”

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confidence: 99%

An exploration of the reactivity of singlet oxygen with biomolecular constituents

Marchetti

Karsili

2016

Chem. Commun.

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The thermal reaction between biomolecules and singlet oxygen ((1)O2) is important for rendering the genetic material within toxic cells inactive. Here we present results obtained from state-of-the-art multi-reference computational methods that reveal the mechanistic details of the reaction between (1)O2 and two exemplary biomolecular systems: guanine (Gua) and histidine (His). The results highlight the splitting of the doubly degenerate (1)Δg state of O2 upon complexation and the essentially barrierless potential energy profile of the thermally allowed cycloaddition reaction when the O2 molecule is in its lower energy (1)Δg state.

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Role of Distance in Singlet Oxygen Applications: A Model System

Cited by 45 publications

References 53 publications

Porphyrin-Induced Protein Oxidation and Aggregation as a Mechanism of Porphyria-Associated Cell Injury

Porphyrin-Induced Protein Oxidation and Aggregation as a Mechanism of Porphyria-Associated Cell Injury

Potassium Iodide Potentiates Broad-Spectrum Antimicrobial Photodynamic Inactivation Using Photofrin

An exploration of the reactivity of singlet oxygen with biomolecular constituents

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