Factors Affecting Virus Photoinactivation by a Series of Phenothiazine Dyes

Wagner, Stephen J.; Skripchenko, Andrey; Robinette, Daniel; Foley, James W.; Cincotta, Louis

doi:10.1111/j.1751-1097.1998.tb05208.x

Cited by 132 publications

(118 citation statements)

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“…18 Compound 10 was subsequently treated with an oxidizing agent, potassium dichromate, forming the semiquinonide ion in situ, 19 which in turn was able to react with either 1,6-or 1,7-dihydroxynaphthalene (6a and b), respectively (Scheme 2). The resultant phenothiazine dyes (11a and b) were then alkylated at room temperature with trimethylsilylethanol protected bromobutyric acid.…”

Section: Synthesismentioning

confidence: 99%

Probing lipid- and drug-binding domains with fluorescent dyes

Black

Stanley

Filipp

et al. 2008

Bioorganic & Medicinal Chemistry

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A series of 2-and 3-OH Nile red dyes was prepared in order to generate water-soluble probes that could be used to probe lipid binding to proteins. Various substitutions in positions 2-/3-, 6-, and 7-shifted wavelengths while maintaining the environmental sensitivity of Nile red. In order to increase the solubility of the dyes in aqueous solutions, we attached butyric acid groups to the 2-or 3-OH position. In addition, phenothiazine dyes, which exhibited particularly long excitation properties, were synthesized and tested for the first time. All dyes showed Stoke's shifts of 70-100 nm and changes in excitation and emission of over 100 nm, depending on the hydrophobicity of the environment. Binding studies with bovine serum albumin and the non-specific lipid transfer protein SCP2 revealed emission changes of more than 30 nm upon binding to the protein and a five-fold increase in emission intensity. Titration of the dye-loaded proteins with various lipids or drugs replaced the dye and thereby reversed the shift in wavelength intensity. This allowed us to estimate the lipid binding affinity of the investigated proteins. For SCP2, isothermal calorimetry (ITC) data verified the titration experiments. NMR titration experiments of SCP2 with Nile red 2-O-butyric acid (1a) revealed that the dye is bound within the lipid binding pocket and competes with lipid ligands for this binding site. These results give valuable insight into lipid and drug transport by proteins outside and inside cells.

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Section: Synthesismentioning

confidence: 99%

Probing lipid- and drug-binding domains with fluorescent dyes

Black

Stanley

Filipp

et al. 2008

Bioorganic & Medicinal Chemistry

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“…12) There is no data about the conversion of dimer to monomer on addition of virus particles instead of naked nucleic acid. Although a singlet oxygen yield of DMMB is 50% greater than that of MB, virus inactivation by DMMB is roughly 10 times greater than that by MB.…”

Section: Discussionmentioning

confidence: 99%

“…Dimers predominate as higher concentrations. 12) In order to inactivate R17 with a 580 nm light, the DMMB concentration had to be increased, although the dye concentration was below 0.1 mM in the experiment in Fig. 1.…”

Section: R17mentioning

confidence: 99%

“…In other experiments, the requirement of oxygen for virus photoinactivation by DMMB was demonstrated by the failure to achieve inactivation in samples bubbled with nitrogen. 12) The absorption spectrum of DMMB in aqueous solutions has two peaks, which represent light absorption from the monomer and dimer forms. 12) Activation of the dimer (max 590 nm), in contrast to monomer, resulted in virus photoinactivation with photooxidation of hemoglobin to methemoglobin (Met-Hb).…”

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confidence: 99%

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Involvement of Reactive Oxygen Species in Hemoglobin Oxidation and Virus Inactivation by 1,9-Dimethylmethylene Blue Phototreatment.

Hirayama

Wagner

Abe

et al. 2001

Biological & Pharmaceutical Bulletin

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The viral safety of blood products has been significantly enhanced as a consequence of improvements in donor screening. However, there are still measurable risks of viral transmission through blood products.1,2) Therefore, processes for the removal and/or inactivation of viruses may represent an additional level of safety for these biological materials.Hemoglobin derived from human red blood cells is being used to develop a variety of artificial oxygen carriers. [3][4][5] Out-dated red cells for transfusion are an important source of human hemoglobin for the development of artificial oxygen carriers. The usual techniques for virus removal or inactivation, respectively, in stroma-free hemoglobin (SFH) are filtration and heat-treatment. [6][7][8] However, a combination of at least two techniques, which have different mechanisms of action, is important for complete elimination. This is the approach that has been adopted for the sterilization of a variety of pooled plasma derivatives and could have implications for a pooled hemoglobin product.Photosensitizers have been utillized for virus inactivation of blood products.9,10) We have previously reported on virus photoinactivation in SFH by 1,9-dimethylmethylene blue (DMMB).11) Vesicular stomatitis virus (VSV) was inactivatedϾ6 log 10 by DMMB without Met-Hb formation using 1 mM DMMB and red (655 nm) LED light.11) These conditions favor activation of monomer DMMB, which has an absorption peak of ca. 650 nm. In other experiments, the requirement of oxygen for virus photoinactivation by DMMB was demonstrated by the failure to achieve inactivation in samples bubbled with nitrogen.12)The absorption spectrum of DMMB in aqueous solutions has two peaks, which represent light absorption from the monomer and dimer forms.12) Activation of the dimer (max 590 nm), in contrast to monomer, resulted in virus photoinactivation with photooxidation of hemoglobin to methemoglobin (Met-Hb).11) It was speculated that compared with the dimer, the monomer of DMMB has high affinity to nucleic acids and so inactivates virus without inducing Met-Hb formation. However, why Met-Hb forms on exposure to activated dimer but not monomer may also be explained by a difference in the reactive oxygen species (ROS) involved in the four events (virus inactivation by monomer DMMB, virus inactivation by dimer DMMB, Met-Hb formation by monomer DMMB and Met-Hb formation by dimer DMMB). Methylene blue (MB) is known to produce not only singlet oxygen but also other ROS. 13,14) Therefore, DMMB, which is a derivative of MB, may also produce ROS other than singlet oxygen. In order to clarify which ROS are involved in virus inactivation and Met-Hb formation by activated monomer or dimer DMMB, the extent of the inactivation and formation in the presence or absence of ROS scavengers, quenchers or enhancer was evaluated. MATERIALS AND METHODSVirus Assays Bacteriophage R17 and its host, Escherichia coli Hfr C, were obtained from David Cook (Cerus Corporation, Concord, CA, U.S.A.). The plaque assay for bacteriophage R17 ...

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“…However, where cell penetration is required, the hydrophilic nature of methylene blue is disadvantageous, and more lipophilic molecules may be more successful -for example in intracellular virus inactivation in red blood cells (30). Among several physical and chemical properties tested, the affinity of a specific photosensitiser for viral nucleic acid seems to best correlate with its virus photokilling efficiency (31).…”

Section: Photoantimicrobialsmentioning

confidence: 99%