DNA-psoralen: Single-molecule experiments and first principles calculations

Rocha, M. S.; Lúcio, A. D.; Alexandre, Simone S.; Nunes, R. W.; Mesquita, O. N.

doi:10.1063/1.3276555

Cited by 23 publications

(37 citation statements)

References 20 publications

(24 reference statements)

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“…Such behavior of the persistence length appears to be a general property of DNA‐intercalator complexes when stretched under the force regime of

F <

5 pN . In fact, the same qualitative behavior was previously verified under our experimental conditions for the intercalators ethidium bromide, daunomycin, psoralen, diaminobenzidine and for the bis‐intercalator gelred . As detailed discussed in Ref.…”

Section: Resultssupporting

confidence: 88%

“…In addition, observe that the data obtained in the Tris‐HCl buffer presents the typical shape observed for most intercalators . The data obtained in the PBS buffer, on the other hand, exhibits a slightly sigmoidal shape which indicates that another binding mode may exist besides intercalation or/and significant cooperativity can exist between the ligand molecules …”

Section: Resultsmentioning

confidence: 70%

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DNA‐doxorubicin interaction: New insights and peculiarities

2016

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We have investigated the interaction of the DNA molecule with the anticancer drug doxorubicin (doxo) by using three different experimental techniques: single molecule stretching, single molecule imaging, and dynamic light scattering. Such techniques allowed us to get new insights on the mechanical behavior of the DNA-doxo complexes as well as on the physical chemistry of the interaction. First, the contour length data obtained from single molecule stretching were used to extract the physicochemical parameters of the DNA-doxo interaction under different buffer conditions. This analysis has proven that the physical chemistry of such interaction can be modulated by changing the ionic strength of the surrounding buffer. In particular we have found that at low ionc strengths doxo interacts with DNA by simple intercalation (no aggregation) and/or by forming bound dimers. For high ionic strengths, otherwise, doxo-doxo self-association is enhanced, giving rise to the formation of bound doxo aggregates composed by 3 to 4 molecules along the double-helix. On the other hand, the results obtained for the persistence length of the DNA-doxo complexes is strongly force-dependent, presenting different behaviors when measured with stretching or non-stretching techniques.

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“…Such behavior of the persistence length appears to be a general property of DNA‐intercalator complexes when stretched under the force regime of

F <

Section: Resultssupporting

confidence: 88%

Section: Resultsmentioning

confidence: 70%

DNA‐doxorubicin interaction: New insights and peculiarities

2016

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“…In fact, the general behavior of the persistence length A shown in Fig. 1 was previously verified by our group for the intercalators ethidium bromide (EtBr), daunomycin, psoralen and diaminobenzidine under nearly similar experimental conditions [26], [24], [27], [23], by using optical Fig. 1 Persistence length A as a function of ligand total concentration in the sample C T .…”

Section: Stretching Experimentssupporting

confidence: 65%

Characterizing the interaction between DNA and GelRed fluorescent stain

Crisafuli

Rocha

2014

Eur Biophys J

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We have performed single molecule stretching experiments and dynamic light scattering (DLS) in order to characterize the interaction between the DNA molecule and the fluorescent stain GelRed. The results from single molecule stretching show that the persistence length of the DNA-GelRed complexes increases as the ligand concentration increases up to some critical concentration, then decreasing for higher concentrations. The contour length of the complexes, on the other hand, increases monotonically as a function of GelRed concentration, suggesting that intercalation is the main binding mechanism. In order to characterize the physical chemistry of the interaction, we use the McGhee-von Hippel binding isotherm to extract the physicochemical parameters of the interaction from the contour length data. Such analysis has allowed us to conclude that the GelRed stain is in fact a bis-intercalator. In addition, DLS experiments were performed to study the changes of the effective size of the DNA-GelRed complexes, measured by the hydrodynamic radius, as a function of ligand concentration. We found a qualitative agreement between the results obtained from the two techniques by comparing the behaviors of the hydrodynamics radius and the radius of gyration, since this last quantity can be expressed as a function of mechanical parameters determined from the stretching experiments.

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“…Recently our group has studied in detail the changes in the persistence and contour lengths of DNA complexes formed with various intercalating molecules [75][76][77]94,133 , by using optical tweezers in a very low force regime (F < 2 pN). We reported an abrupt structural transition in the persistence length due to drug intercalation, which is probably related to a partial denaturation of the DNA molecule due to the pulling force used to stretch the complexes 76,77,133,147 . The contour length, otherwise, does not present such a transition, increasing monotonically with drug concentration until saturation.…”

Section: B Intercalatorsmentioning

confidence: 99%

“…When there is no illumination at the sample, however, psoralen interacts with DNA by intercalative binding -see next section. The effects of covalent binding on the mechanical properties of the DNA-psoralen complexes were recently studied 94,133 . In particular, it was shown that the contour and persistence lengths of the complexes depend on the psoralen concentration and on the exposure time to UVA light 133 .…”

Section: A Covalent Ligandsmentioning

confidence: 99%

Extracting physical chemistry from mechanics: a new approach to investigate DNA interactions with drugs and proteins in single molecule experiments

Rocha

2015

Integr. Biol.

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116

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In this review we focus on the idea of establishing connections between the mechanical properties of DNAligand complexes and the physical chemistry of DNA-ligand interactions. This type of connection is interesting because it opens the possibility of performing a robust characterization of such interactions by using only one experimental technique: single molecule stretching. Furthermore, it also opens new possibilities in comparing results obtained by very different approaches, in special when comparing single molecule techniques to ensemble-averaging techniques. We start the manuscript reviewing important concepts of the DNA mechanics, from the basic mechanical properties to the Worm-Like Chain model. Next we review the basic concepts of the physical chemistry of DNA-ligand interactions, revisiting the most important models used to analyze the binding data and discussing their binding isotherms. Then, we discuss the basic features of the single molecule techniques most used to stretch the DNA-ligand complexes and to obtain force × extension data, from which the mechanical properties of the complexes can be determined. We also discuss the characteristics of the main types of interactions that can occur between DNA and ligands, from covalent binding to simple electrostatic driven interactions. Finally, we present a historical survey on the attempts to connect mechanics to physical chemistry for DNA-ligand systems, emphasizing a recently developed fitting approach useful to connect the persistence length of the DNA-ligand complexes to the physicochemical properties of the interaction. Such approach in principle can be used for any type of ligand, from drugs to proteins, even if multiple binding modes are present.

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DNA-psoralen: Single-molecule experiments and first principles calculations

Cited by 23 publications

References 20 publications

DNA‐doxorubicin interaction: New insights and peculiarities

DNA‐doxorubicin interaction: New insights and peculiarities

Characterizing the interaction between DNA and GelRed fluorescent stain

Extracting physical chemistry from mechanics: a new approach to investigate DNA interactions with drugs and proteins in single molecule experiments

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