The antibiotics known as bleomycins constitute a family of natural products clinically employed for the treatment of a wide spectrum of cancers. The drug acts as an antitumor agent by virtue of the ability of a metal complex of the antibiotic to cleave DNA. Bleomycins are differentiated by their C-terminal regions. Previous structural studies involving metal-bleomycin-DNA triads have allowed the identification of the bithiazole-(C-terminus substituent) segment in this molecule as the one that most closely interacts with DNA. Three different modes of binding of metallo-bleomycins to DNA (partial or total intercalation of the bithiazole unit between DNA bases, or binding to the minor groove) have been proposed in the literature. The therapeutic use of bleomycin is frequently associated with the development of pulmonary fibrosis. The severity of this side effect has been attributed to the C-terminus of the antibiotic by some researchers. The degree of pulmonary toxicity of bleomycin-A2 and -A5, were found to be higher than those of bleomycin-B2 and peplomycin. Since the introduction of Blenoxane to clinical medicine in 1972, attempts have been made at modifying the basic bleomycin structure at the C-terminus to improve its therapeutic index. However, the pharmacological and toxicological importance of particular C-termini on bleomycin remains unclear. The present study was designed to determine the effect of Zn(II)bleomycin-A2, -A5, -B2, and Zn(II)peplomycin on the structure of a DNA hairpin containing the 5′-GC-3′ binding site. We provide evidence that different Zn(II)bleomycins affect the structure of the tested DNA segment in different fashions.

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Bleomycins are a group of glycopeptide antibiotics synthesized by Streptomyces verticillus that are widely used for the treatment of various neoplastic diseases. These antibiotics have the ability to chelate a metal center, mainly Fe(II), and cause site-specific DNA cleavage. Bleomycins are differentiated by their C-terminal regions. Although this antibiotic family is a successful course of treatment for some types of cancers, it is known to cause pulmonary fibrosis. Previous studies have identified that bleomycin-related pulmonary toxicity is linked to the C-terminal region of these drugs. This region has been shown to closely interact with DNA. We examined the binding of Zn(II)peplomycin and Zn(II)bleomycin-A2 to a DNA hairpin of sequence 5’-CCAGTATTTTTACTGG-3’, containing the binding site 5’-GT-3’, and compare the results with those obtained from our studies of the same MBLMs bound to a DNA hairpin containing the binding site 5’-GC-3’. We provide evidence that the DNA base sequence has a strong impact in the final structure of the drug-target complex.

Bleomycins are antitumor antibiotics that can chelate a metal center and cause site-specific DNA cleavage at 5’-Gpyrimidine-3’ regions of DNA. These antibiotics are successful in the treatment of various cancers, but are known to cause pulmonary fibrosis to patients under bleomycin regimes. Substantial research has resulted in the development of over 300 bleomycin analogs, aiming to improve the therapeutic index of the drug. Previous studies have proposed that the lung toxicity caused by bleomycin is related to the C-terminal regions of these drugs, which have been shown to closely interact with DNA in metal-bleomycin-DNA complexes. Some of the research studying metallo-bleomycin-DNA interactions have suggested three different binding modes of the metal form of the drug to DNA, including total and/or partial intercalation, and minor groove binding. However, there is still lack of consensus regarding this matter, and solid conclusions on the subject have not yet been established. Previously we investigated the diverse levels of disruption caused to DNA hairpins containing 5’-GC-3’ and 5’-GT-3’ binding sites, which are consequence of the binding of bleomycins with different C-termini. The results of these investigation indicate that both the DNA-binding site and the bleomycin C-termini have an impact on the final conformations of drug and target. The present study focuses on the structural alterations exhibited by Zn(II)bleomycin-A2, -B2, -A5 and Zn(II)peplomycin upon binding to DNA hairpins containing 5’-GC-3’ and 5’-GT-3’ binding sites. Evidence that each Zn(II)bleomycin is structurally affected depending on both its C-terminus and the DNA-binding site present in the hairpin is provided.

In this work, nuclear magnetic resonance (NMR) spectroscopy is used to investigate surfactant phase behavior relevant to chemical enhanced oil recovery. The effect of the solution electrical conductivity on the NMR signals was corrected using reference spectra of known conductivity. This allowed us to develop a semi-quantitative method to estimate the surfactant concentration by correlating it with either integrated NMR peaks or intensity of selected surfactant signal peaks. A distinct change in the slope of the assumed linear relationship between signal intensity and surfactant concentration was observed as the surfactant concentrations were increased. This was attributed to the progressive surfactant aggregation in solution. This result can be used as an alternative method to estimate the critical micelle concentration (CMC) of surfactants. NMR spectra were collected for individual surfactants and their combinations in a variety of saline aqueous solutions. Our results were compared to estimates obtained through more traditional ultraviolet–visible (UV–vis) spectroscopy and surface tension measurements. Consistency between NMR and surface tension estimates was found. CMC values determined through UV–vis were similar, although not quite the same as those of the other two techniques. Similarly, the NMR signals were used to estimate surfactant adsorption in the rock in the so-called static adsorption experiments, in which ground rock is exposed to a surfactant solution of known initial concentration. The results obtained show that NMR offers a powerful alternative to more frequently used methods to estimate not only CMC but also surfactant adsorption, particularly when multiple surfactants are present in aqueous solution.