Binding of anti-inflammatory drug indomethacin with cyclodextrin and DNA: solubility, spectroscopic, and voltammetric studies

2001 ◽  
Vol 79 (10) ◽  
pp. 1431-1438 ◽  
Author(s):  
I S Shehatta ◽  
M S Ibrahim
Keyword(s):  
Hydrophobic Interactions ◽  
Double Helix ◽  
Electrochemical Behaviour ◽  
Binding Constants ◽  
Base Pairs ◽  
Inflammatory Drug ◽  
Voltammetric Studies ◽  
Anti Inflammatory ◽  
Dna Double Helix ◽  
Ct Dna

The interaction of the anti-inflammatory drug indomethacin (IMC) with α-, β-cyclodextrins (CDs) and calf thymus deoxyribonucleic acid (ct-DNA) have been investigated in the Britton-Robinson (BR) buffer (pH = 7.2) using solubility, spectroscopic, and voltammetric methods. The measurements show that the IMC molecule, acting as an intercalator, is inserted, from the p-chlorobenzoyl part, into the cavity of the cyclodextrins as well as into the base-stacking domain of the ct-DNA double helix. Upon addition of β-CD in a buffered IMC solution, the solubility of IMC increases and the Gibbs free energies of transfer of the drug from aqueous solution to the cavity of β-CD are negative and increase negatively with increasing β-CD concentration. The interaction of IMC with CDs and ct-DNA causes hypochromism and bathochromic shifts in the absorption spectra, along with pronounced changes in the electrochemical behaviour of the drug. The stoichiometry of complexes formed in solution is inferred to be 1:1. The binding constants were calculated from the increase of the solubility, the strong hypochromism, and the decrease in peak current of IMC upon the addition of the host molecules. IMC has a higher affinity for β-CD than for α-CD, as the IMC–β-CD interaction is the most exergonic. Binding is interpreted in terms of the intercalative (hydrophobic) interactions with the ct-DNA helix (i.e., the stacked base pairs) or within CD cavity.Key words: cyclodextrin, ct-DNA, anti-inflammatory drug, indomethacin, binding constant, solubility, spectra, voltammetry.

The unique structure of A-tracts and intrinsic DNA bending

2009 ◽  
Vol 42 (1) ◽  
pp. 41-81 ◽  
Author(s):  
Tali E. Haran ◽  
Udayan Mohanty
Keyword(s):  
Current Knowledge ◽  
Double Helix ◽  
Dna Bending ◽  
Helical Axis ◽  
Base Pairs ◽  
Regulatory Regions ◽  
Unique Structure ◽  
Distinct Structure ◽  
Global Curvature ◽  
Dna Double Helix

AbstractShort runs of adenines are a ubiquitous DNA element in regulatory regions of many organisms. When runs of 4–6 adenine base pairs (‘A-tracts’) are repeated with the helical periodicity, they give rise to global curvature of the DNA double helix, which can be macroscopically characterized by anomalously slow migration on polyacrylamide gels. The molecular structure of these DNA tracts is unusual and distinct from that of canonical B-DNA. We review here our current knowledge about the molecular details of A-tract structure and its interaction with sequences flanking them of either side and with the environment. Various molecular models were proposed to describe A-tract structure and how it causes global deflection of the DNA helical axis. We review old and recent findings that enable us to amalgamate the various findings to one model that conforms to the experimental data. Sequences containing phased repeats of A-tracts have from the very beginning been synonymous with global intrinsic DNA bending. In this review, we show that very often it is the unique structure of A-tracts that is at the basis of their widespread occurrence in regulatory regions of many organisms. Thus, the biological importance of A-tracts may often be residing in their distinct structure rather than in the global curvature that they induce on sequences containing them.

scholarly journals Use of Nucleic Acid Analogs for the Study of Nucleic Acid Interactions

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Shu-ichi Nakano ◽  
Masayuki Fujii ◽  
Naoki Sugimoto
Keyword(s):  
Nucleic Acid ◽  
Base Pair ◽  
Double Helix ◽  
Nucleoside Analogs ◽  
Structural Analog ◽  
Base Pairs ◽  
Nucleic Acid Analogs ◽  
Dna Double Helix ◽  
Nucleic Acid Interactions ◽  
Site Selective

Unnatural nucleosides have been explored to expand the properties and the applications of oligonucleotides. This paper briefly summarizes nucleic acid analogs in which the base is modified or replaced by an unnatural stacking group for the study of nucleic acid interactions. We also describe the nucleoside analogs of a base pair-mimic structure that we have examined. Although the base pair-mimic nucleosides possess a simplified stacking moiety of a phenyl or naphthyl group, they can be used as a structural analog of Watson-Crick base pairs. Remarkably, they can adopt two different conformations responding to their interaction energies, and one of them is the stacking conformation of the nonpolar aromatic group causing the site-selective flipping of the opposite base in a DNA double helix. The base pair-mimic nucleosides can be used to study the mechanism responsible for the base stacking and the flipping of bases out of a nucleic acid duplex.

5-Aza-7-deaza-2′-deoxyguanosine and 2′-Deoxycytidine Form Programmable Silver-Mediated Base Pairs with Metal Ions in the Core of the DNA Double Helix

2018 ◽  
Vol 24 (35) ◽  
pp. 8883-8892 ◽  
Author(s):  
Xiurong Guo ◽  
Peter Leonard ◽  
Sachin A. Ingale ◽  
Jiang Liu ◽  
Hui Mei ◽  
...  
Keyword(s):  
Metal Ions ◽  
Double Helix ◽  
Base Pairs ◽  
The Core ◽  
Dna Double Helix

scholarly journals Affinity studies of hypocrellin B and mono-cysteine substituted hypocrellin B with CT-DNA using spectroscopic methods

2005 ◽  
Vol 19 (5,6) ◽  
pp. 259-266 ◽  
Author(s):  
Shaohua Wei ◽  
Jiahong Zhou ◽  
Yuying Feng ◽  
Deyin Huang ◽  
Xuesong Wang ◽  
...  
Keyword(s):  
Deoxyribonucleic Acid ◽  
Double Helix ◽  
Cd Spectroscopy ◽  
Base Stacking ◽  
Calf Thymus ◽  
Visible Spectra ◽  
Hypocrellin B ◽  
Uv Visible ◽  
Dna Double Helix ◽  
Ct Dna

The interaction of anticancer drug hypocrellin B (HB) and mono-cysteine substituted hypocrellin B (MCHB) with calf thymus deoxyribonucleic acid (CT-DNA) has been investigated using spectral methods. The results of UV–visible spectra showed that the HB and MCHB can intercalate into the base-stacking domain of the CT-DNA double helix. Further studies based on fluorescence spectroscopy and circular dichroism (CD) spectroscopy also supported the intercalation mechanism.

scholarly journals DNA information: from digital code to analogue structure

2012 ◽  
Vol 370 (1969) ◽  
pp. 2960-2986 ◽  
Author(s):  
A. A. Travers ◽  
G. Muskhelishvili ◽  
J. M. T. Thompson
Keyword(s):  
Dimensional Space ◽  
Double Helix ◽  
Three Dimensional ◽  
Base Pairs ◽  
Nucleosome Core ◽  
Histone Octamer ◽  
Regulatory Mode ◽  
Sequence Periodicity ◽  
Recent Developments ◽  
Dna Double Helix

The digital linear coding carried by the base pairs in the DNA double helix is now known to have an important component that acts by altering, along its length, the natural shape and stiffness of the molecule. In this way, one region of DNA is structurally distinguished from another, constituting an additional form of encoded information manifest in three-dimensional space. These shape and stiffness variations help in guiding and facilitating the DNA during its three-dimensional spatial interactions. Such interactions with itself allow communication between genes and enhanced wrapping and histone–octamer binding within the nucleosome core particle. Meanwhile, interactions with proteins can have a reduced entropic binding penalty owing to advantageous sequence-dependent bending anisotropy. Sequence periodicity within the DNA, giving a corresponding structural periodicity of shape and stiffness, also influences the supercoiling of the molecule, which, in turn, plays an important facilitating role. In effect, the super-helical density acts as an analogue regulatory mode in contrast to the more commonly acknowledged purely digital mode. Many of these ideas are still poorly understood, and represent a fundamental and outstanding biological question. This review gives an overview of very recent developments, and hopefully identifies promising future lines of enquiry.

scholarly journals Solution structure of a DNA double helix with consecutive metal-mediated base pairs

2010 ◽  
Vol 2 (3) ◽  
pp. 229-234 ◽  
Author(s):  
Silke Johannsen ◽  
Nicole Megger ◽  
Dominik Böhme ◽  
Roland K. O. Sigel ◽  
Jens Müller
Keyword(s):  
Solution Structure ◽  
Double Helix ◽  
Base Pairs ◽  
Dna Double Helix

scholarly journals Destabilization of DNA duplexes by oxidative damage at guanine: implications for lesion recognition and repair

2008 ◽  
Vol 5 (suppl_3) ◽  
pp. 191-198 ◽  
Author(s):  
Supat Jiranusornkul ◽  
Charles A Laughton
Keyword(s):  
Oxidative Damage ◽  
Structural Changes ◽  
Double Helix ◽  
Dependent Manner ◽  
Dna Duplexes ◽  
Lesion Site ◽  
Base Pairs ◽  
Energetic Analysis ◽  
Dynamics Simulations ◽  
Dna Double Helix

We have used molecular dynamics simulations to study the structure and dynamics of a range of DNA duplexes containing the 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapydG) lesion that can result from oxidative damage at guanine. Compared to the corresponding undamaged DNA duplexes, FapydG-containing duplexes show little gross structural changes—the damaged base remains stacked in to the DNA double helix and retains hydrogen bonds to its cytosine partner. However, the experimentally observed reduction in DNA stability that accompanies lesion formation can be explained by a careful energetic analysis of the simulation data. Irrespective of the nature of the base pairs on either side of the lesion site, conversion of a guanine to a FapydG base results in increased dynamical flexibility in the base (but not in the DNA as a whole) that significantly weakens its hydrogen-bonding interactions. Surprisingly, the stacking interactions with its neighbours are not greatly altered. The formamido group adopts a non-planar conformation that can interact significantly and in a sequence-dependent manner with its 3′-neighbour. We conclude that the recognition of FapydG lesions by the repair protein formamidopyrimidine-DNA glycosylase probably does not involve the protein capturing an already-extrahelical FapydG base, but rather it relies on detecting alterations to the DNA structure and flexibility created by the lesion site.

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