Drug—nucleic acid interaction: X-ray crystallographic determination of an ethidium—dinucleoside monophosphate crystalline complex, ethidium: 5-iodouridylyl(3'-5')adenosine

1975 ◽  
Vol 272 (915) ◽  
pp. 137-146 ◽  
Keyword(s):  
Nucleic Acid ◽  
Double Helix ◽  
Monoclinic Space Group ◽  
Sequence Specificity ◽  
Acid Interaction ◽  
Base Pairs ◽  
Crystalline Complex ◽  
Structural Explanation ◽  
Solution Studies ◽  
Model Drug

The intercalative trypanosomal drug, ethidium bromide, forms a crystalline complex with the dinucleoside monophosphate, 5-iodouridylyl(3'-5')adenosine (iodoUpA). These crystals are monoclinic, space group C2, with unit cell dimensions a =2.845nm, b = 1.354 nm, c = 3.413nm, β =98.6°. The structure has been solved to atomic resolution by Patterson and Fourier methods, and refined by full matrix least squares to a residual of 0.20 on 2017 observed reflexions. The asymmetric unit con­tains two ethidium molecules, two iodoUpA molecules, twenty water molecules and four methanol molecules, a total of 156 atoms excluding hydrogens. The two iodoUpA molecules are held together by adenine-uracil Watson-Crick base-pairing. Adjacent base-pairs within this paired iodoUpA structure and between neighbouring iodoUpA molecules in adjoining unit cells are separated by 0.68 nm. This separation results from intercalative binding by one ethidium molecule and stacking by the other ethidium molecule above and below the base-pairs. Non-crystallographic twofold symmetry is utilized in this model drug-nucleic acid interaction, the intercalative ethidium molecule being oriented such that its phenyl and ethyl groups lie in the nar­row groove of the miniature nucleic acid double helix. Solution studies have indicated a marked sequence specificity for ethidium-dinucleotide interactions and a probable structural explanation for this has been provided by this study.

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.

scholarly journals A DNA G-quadruplex/i-motif hybrid

2019 ◽  
Author(s):  
Betty Chu ◽  
Daoning Zhang ◽  
Paul J Paukstelis
Keyword(s):  
Tandem Repeats ◽  
Double Helix ◽  
Structural Diversity ◽  
Hybrid Structure ◽  
Structural Motif ◽  
Base Pairs ◽  
Independent Sequence ◽  
Solution Studies ◽  
G Quadruplex

Abstract DNA can form many structures beyond the canonical Watson–Crick double helix. It is now clear that noncanonical structures are present in genomic DNA and have biological functions. G-rich G-quadruplexes and C-rich i-motifs are the most well-characterized noncanonical DNA motifs that have been detected in vivo with either proscribed or postulated biological roles. Because of their independent sequence requirements, these structures have largely been considered distinct types of quadruplexes. Here, we describe the crystal structure of the DNA oligonucleotide, d(CCAGGCTGCAA), that self-associates to form a quadruplex structure containing two central antiparallel G-tetrads and six i-motif C–C+ base pairs. Solution studies suggest a robust structural motif capable of assembling as a tetramer of individual strands or as a dimer when composed of tandem repeats. This hybrid structure highlights the growing structural diversity of DNA and suggests that biological systems may harbor many functionally important non-duplex structures.

scholarly journals A DNA G-quadruplex/i-motif hybrid

2019 ◽  
Author(s):  
Betty Chu ◽  
Daoning Zhang ◽  
Paul J. Paukstelis
Keyword(s):  
Tandem Repeats ◽  
Double Helix ◽  
Structural Diversity ◽  
Hybrid Structure ◽  
Structural Motif ◽  
Base Pairs ◽  
Independent Sequence ◽  
Solution Studies ◽  
G Quadruplex

AbstractDNA can form many structures beyond the canonical Watson-Crick double helix. It is now clear that noncanonical structures are present in genomic DNA and have biological functions. G-rich G-quadruplexes and C-rich i-motifs are the most well-characterized noncanonical DNA motifs that have been detected in vivo with either proscribed or postulated biological roles. Because of their independent sequence requirements, these structures have largely been considered distinct types of quadruplexes. Here, we describe the crystal structure of the DNA oligonucleotide, d(CCAGGCTGCAA), that self-associates to form a quadruplex structure containing two central antiparallel G-tetrads and six i-motif C-C+ base pairs. Solution studies suggest a robust structural motif capable of assembling as a tetramer of individual strands or as a dimer when composed of tandem repeats. This hybrid structure highlights the growing structural diversity of DNA and suggests that biological systems may harbor many functionally important non-duplex structures.

Nucleic Acid Interaction and Photoluminescent Properties of Acylhydrazone and Its Mn(II), Co(II), Cu(II), Zn(II) and Cd(II) Complexes

2021 ◽  
Author(s):  
M. Sennappan ◽  
P. Murali Krishna ◽  
Praveen B. Managutti ◽  
Sumitra N. Mangasuli ◽  
S. Malini
Keyword(s):  
Nucleic Acid ◽  
Acid Interaction

scholarly journals Base pairing structure in the poly d(G-T) double helix: wobble base pairs

1978 ◽  
Vol 5 (6) ◽  
pp. 1955-1970 ◽  
Author(s):  
Thomas A. Early ◽  
John Olmsted ◽  
David R. Kearns ◽  
Axel G. Lezius
Keyword(s):  
Double Helix ◽  
Base Pairing ◽  
Base Pairs

Mercury Electrodes in Nucleic Acid Electrochemistry: Sensitive Analytical Tools and Probes of DNA Structure. A Review

2004 ◽  
Vol 69 (4) ◽  
pp. 715-747 ◽  
Author(s):  
Miroslav Fojta
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Double Helix ◽  
Dna Structure ◽  
Electrochemical Analysis ◽  
Label Free ◽  
Helix Formation ◽  
Mercury Electrodes ◽  
Dna Strand ◽  
Dna Double Helix

This review is devoted to applications of mercury electrodes in the electrochemical analysis of nucleic acids and in studies of DNA structure and interactions. At the mercury electrodes, nucleic acids yield faradaic signals due to redox processes involving adenine, cytosine and guanine residues, and tensammetric signals due to adsorption/desorption of polynucleotide chains at the electrode surface. Some of these signals are highly sensitive to DNA structure, providing information about conformation changes of the DNA double helix, formation of DNA strand breaks as well as covalent or non-covalent DNA interactions with small molecules (including genotoxic agents, drugs, etc.). Measurements at mercury electrodes allow for determination of small quantities of unmodified or electrochemically labeled nucleic acids. DNA-modified mercury electrodes have been used as biodetectors for DNA damaging agents or as detection electrodes in DNA hybridization assays. Mercury film and solid amalgam electrodes possess similar features in the nucleic acid analysis to mercury drop electrodes. On the contrary, intrinsic (label-free) DNA electrochemical responses at other (non-mercury) solid electrodes cannot provide information about small changes of the DNA structure. A review with 188 references.

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