A systematic approach toward the analysis of drug–DNA interactions using Raman spectroscopy: The binding of metal‐free bleomycins A
            <sub>2</sub>
            and B
            <sub>2</sub>
            to calf thymus DNA

Rajani, Cynthia; Kincaid, James R.; Petering, David H.

doi:10.1002/1097-0282(1999)52:3<110::aid-bip20>3.0.co;2-#

Cited by 6 publications

(6 citation statements)

References 45 publications

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“…However, ultraviolet RRS is often coupled with off-resonance Raman methods because it cannot provide information on the response of DNA backbone to drug binding. [446][447][448] CARS microscopy can image selected molecular vibrations and conformations in three dimensions with submicrometer spatial resolution upon exploiting a picosecond tunable laser and suitable optical filters. Multifocus excitation using a rotatory-microlens array also enables multispectral imaging.…”

Section: Innovative Developments Of the Raman Methodsmentioning

confidence: 99%

Raman spectroscopy in cell biology and microbiology

Pezzotti

2021

J Raman Spectroscopy

135

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The Raman spectrum of living cells and microorganisms contains highly specific fingerprint‐like signatures, useful in unequivocally identifying different species and interpreting physiological and metabolic responses to environmental stressors. In situ Raman imaging with dedicated highly sensitive instruments can translate selected spectroscopic fingerprints into vivid snapshots of molecular species or specific physiological reactions. Time‐lapse experiments, crucial in characterizing growth‐dependent phenomena and metabolic response to drugs or substrates, are possible because Raman imaging is life compatible. This review covers miscellaneous examples of Raman analyses and imaging of eukaryotic cells, bacteria, and viruses. Fundamental microbiological analyses covered here include (i) identification of different species of cells, bacteria, and viruses; (ii) characterization of the metabolic responses of cells and bacteria to different substrates; (iii) time‐lapse analyses of cell metabolic reactions upon viral inoculation; (iv) chemical imaging of axon sprouting in neuronal cells; and (v) visualization of the myelinating activity of living Schwann cells in coculture with neuronal cells. The spectroscopic findings displayed here, which are based on a machine learning approach applied to Raman analysis and imaging, demonstrate the invaluable potential for Raman spectroscopy in biophysics research.

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Section: Innovative Developments Of the Raman Methodsmentioning

confidence: 99%

Raman spectroscopy in cell biology and microbiology

Pezzotti

2021

J Raman Spectroscopy

135

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“…This additional dimension can be accessed by off-resonance Raman methods, provided that the strong absorption and fluorescence mechanisms of many DNA-binding drugs can be circumvented. Rajani et al 187,188 used conventional Raman spectroscopy to investigate DNA complexes of bleomycin. Two modes of binding with double-stranded DNA were identified, one involving intercalation of the bithiazole moiety and a second consistent with minor groove binding.…”

Section: Drug-dna Complexesmentioning

confidence: 99%

Raman, polarized Raman and ultraviolet resonance Raman spectroscopy of nucleic acids and their complexes

Benevides

Overman

Thomas

2005

J Raman Spectroscopy

204

231

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Applications of Raman spectroscopy to investigate the molecular constituents of nucleic acids were initiated in the late 1960s and soon thereafter progressed to studies of synthetic and native nucleic acids and complex biological assemblies containing either DNA or RNA. Raman applications to nucleic acids have continued to increase in number and diversity up to the present time. This paper attempts to provide an overview of this large body of work, with emphasis on studies carried out during the past decade and focusing on problems of biological interest and significance. The specific Raman methodologies included in this review of nucleic acid applications are (i) conventional Raman spectroscopy (i.e. off-resonance Raman excitation), (ii) ultraviolet resonance Raman (UVRR) spectroscopy, and (iii) polarized Raman microspectroscopy. For each methodology, the experimentally obtained nucleic acid spectrum consists of a number of discrete vibrational bands, most of which can be assigned confidently to a base, sugar or phosphate constituent of the macromolecule and many of which can be employed as sensitive indicators or fingerprints of either local structure, global conformation, intermolecular interaction or molecular dynamics. The applications selected for review include numerous examples from the authors' laboratories. The topics addressed include the influences of base composition, base sequence, superhelical stress and drug ligation on nucleic acid structure and polymorphism, the thermodynamic parameters governing nucleic acid premelting and melting phenomena, the molecular mechanisms and determinants of protein/nucleic acid recognition and the structures and dynamics of nucleic acids in virus assemblies.

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“…The drug is synthesized in the bacterium by modular non-ribosomal peptide synthetases and also polyketide synthases [7]. The compound can be dissected into several regions; the metal binding region, the linker with its small polyketide stretch, the DNA binding site and finally the disaccharide position [8] (Figure 1). The metal-binding domain involves a distorted square pyramidal arrangement, whereby the metal is fixed to the imidazole, deprotonated His amide, pyrimidine, and the primary and secondary amine of the β-aminoalanine residue [9].…”

Section: Introductionmentioning

confidence: 99%

“…The DNA recognition site has been narrowed down to the bithiazole moiety with its cationic tail, like shown for BLM A5 and A2 ( Figure 1). A partial intercalation of BLM with DNA has been proposed even at the physiologically relevant temperature of 30 °C [8]. After binding the metal binding domain and disaccharide units partially stack against each other and display base-specific hydrogen bonding to the minor groove of the DNA [9].…”

Section: Introductionmentioning

confidence: 99%

“…Among a series of transition metal ions that bind to the nitrogen atoms of BLM, like Fe, Co, Cu, etc., the divalent Fe(II) cation is the most important one for causing biological activity [10]. [8,9]. The modular built BLM molecule comprises the DNA binding site, the linker region synthesized by polyketide synthase, the metal binding region with its interacting nitrogen atoms (black circles) and the disaccharide portion (the red circles interact with the minor groove of the DNA).…”

Section: Introductionmentioning

confidence: 99%

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Polyphosphate Reverses the Toxicity of the Quasi-Enzyme Bleomycin on Alveolar Endothelial Lung Cells In Vitro

Müller

Neufurth

Wang

et al. 2021

Cancers

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The anti-cancer antitumor antibiotic bleomycin(s) (BLM) induces athyminic sites in DNA after its activation, a process that results in strand splitting. Here, using A549 human lung cells or BEAS-2B cells lunc cells, we show that the cell toxicity of BLM can be suppressed by addition of inorganic polyphosphate (polyP), a physiological polymer that accumulates and is released from platelets. BLM at a concentration of 20 µg ml−1 causes a decrease in cell viability (by ~70%), accompanied by an increased DNA damage and chromatin expansion (by amazingly 6-fold). Importantly, the BLM-caused effects on cell growth and DNA integrity are substantially suppressed by polyP. In parallel, the enlargement of the nuclei/chromatin in BLM-treated cells (diameter, 20–25 µm) is normalized to ~12 µm after co-incubation of the cells with BLM and polyP. A sequential application of the drugs (BLM for 3 days, followed by an exposure to polyP) does not cause this normalization. During co-incubation of BLM with polyP the gene for the BLM hydrolase is upregulated. It is concluded that by upregulating this enzyme polyP prevents the toxic side effects of BLM. These data might also contribute to an application of BLM in COVID-19 patients, since polyP inhibits binding of SARS-CoV-2 to cellular ACE2.

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A systematic approach toward the analysis of drug–DNA interactions using Raman spectroscopy: The binding of metal‐free bleomycins A ₂ and B ₂ to calf thymus DNA

Cited by 6 publications

References 45 publications

Raman spectroscopy in cell biology and microbiology

Raman spectroscopy in cell biology and microbiology

Raman, polarized Raman and ultraviolet resonance Raman spectroscopy of nucleic acids and their complexes

Polyphosphate Reverses the Toxicity of the Quasi-Enzyme Bleomycin on Alveolar Endothelial Lung Cells In Vitro

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A systematic approach toward the analysis of drug–DNA interactions using Raman spectroscopy: The binding of metal‐free bleomycins A 2 and B 2 to calf thymus DNA

Cited by 6 publications

References 45 publications

Raman spectroscopy in cell biology and microbiology

Raman spectroscopy in cell biology and microbiology

Raman, polarized Raman and ultraviolet resonance Raman spectroscopy of nucleic acids and their complexes

Polyphosphate Reverses the Toxicity of the Quasi-Enzyme Bleomycin on Alveolar Endothelial Lung Cells In Vitro

Contact Info

Product

Resources

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A systematic approach toward the analysis of drug–DNA interactions using Raman spectroscopy: The binding of metal‐free bleomycins A ₂ and B ₂ to calf thymus DNA