scholarly journals Binding of quinomycin antibiotic UK-65,662 to DNA: 1H-n.m.r. studies of drug-inducedchanges in DNA conformation in complexes with d(ACGT)2 and d(GACGTC)2

1994 ◽  
Vol 304 (3) ◽  
pp. 967-979 ◽  
Author(s):  
M S Searle
Keyword(s):  
Hydrogen Bonding ◽  
Nuclear Overhauser Effect ◽  
Drug Binding ◽  
Dna Conformation ◽  
Dna Duplexes ◽  
Base Pairs ◽  
Purine Base ◽  
Nuclear Overhauser ◽  
Nuclear Overhauser Effects

Quinomycin antibiotic UK-65,662 binds selectively to the 5′-CpG-binding sites of the DNA duplexes d(ACGT)2 and d(GACGTC)2; the complexes have been studied in detail by 1H-n.m.r. spectroscopy and molecular-modelling techniques employing nuclear Overhauser effect-restrained energy minimization and molecular dynamics. Whereas the terminal A.T base pairs of the tetamer duplex d(ACGT)2 adopt a stable Hoogsteen alignment (characterized by a syn glycosidic conformation of the purine base), when internalized within the hexamer duplex d(GACGTC)2, the A.T base pairs revert to anti glycosidic torsion angles characteristic of the Watson-Crick hydrogen-bonding scheme. The energetics of base-pair stacking at the terminal 5′-GpA steps of the hexamer complex, with base pairs in the Watson-Crick alignment, are concluded to be important determinants of the adopted conformation, whereas an energetic preference for stacking interactions between terminal Hoogsteen A.T base pairs and the drug quinoline chromophores is evident in the tetramer complex. The internal G.C base pairs in both complexes are highly stabilized, as indicated by the very slow exchange rates of the guanine imino protons; in contrast, the flanking A.T base pairs are no more stable than in the ligand-free DNA duplexes. A large number of intermolecular nuclear Overhauser effects are indicative of many van der Waals contacts and hydrogen-bonding between the antibiotic and the minor groove of the central G.C base pairs in both complexes, indicating that interactions with the G.C base pairs in each duplex are very similar providing the essential features for recognition and tight binding. Despite the difference in the conformation of the A.T base pairs, stacking with the quinoline rings occurs primarily with the adenine bases in both complexes. Relative intensities of intranucleotide versus internucleotide nuclear Overhauser effects indicate that both duplexes are substantially unwound by drug binding (particularly at the CpG step) and this is confirmed by the structure calculations. Both duplexes have ladder-like structures that must lead to significant local distortions of the DNA conformation in vivo.

Conformation of purine mononucleotides by H{H} and P{H} nuclear Overhauser effects

1983 ◽  
Vol 61 (7) ◽  
pp. 1456-1464 ◽  
Author(s):  
H. Santos ◽  
A. V. Xavier ◽  
C.F.G.C. Geraldes
Keyword(s):  
Aqueous Solution ◽  
Nuclear Overhauser Effect ◽  
Coupling Constants ◽  
Glycosidic Bond ◽  
Proton Proton ◽  
Proton Coupling ◽  
Vicinal Proton ◽  
Group A ◽  
Nuclear Overhauser ◽  
Nuclear Overhauser Effects

The proton–proton and phosphorus–proton nuclear Overhauser effect (nOe) of guanosine 5′-monophosphate (5′-GMP) was measured in aqueous solution at different pH values and in the presence of excess LaIII at acid pH. These data and nOe data from the literature for other mononucleotides were used together with vicinal proton–proton coupling constants to investigate the conformations of mononucleotides in aqueous solution, especially their rotational state about the glycosidic bond. Comparison of observed and calculated enhancements using various conformational models for the glycosidic bond gave predominantly anti conformations for 5′-AMP and 5′-GMP and a mixture of syn and anti conformations for 2′-AMP, 2′-GMP, 3′-AMP, and 3′-GMP. Protonation of 5′-GMP at N-7 of the guanine base alters the amplitude of its torsion angle within the anti range. The agreement between the glycosidic nucleotide conformations defined by nOe and by the lanthanide probe method is good but not perfect. As complexation of 5′-GMP with LaIII through the phosphate group has only a small effect on the conformation of its exocyclic group, a comparison of the two methods is justified.

scholarly journals Aniline–phenol recognition: from solution through supramolecular synthons to cocrystals

IUCrJ ◽  
2014 ◽  
Vol 1 (4) ◽  
pp. 228-239 ◽  
Author(s):  
Arijit Mukherjee ◽  
Karuna Dixit ◽  
Siddhartha P. Sarma ◽  
Gautam R. Desiraju
Keyword(s):  
Hydrogen Bonding ◽  
Crystal Engineering ◽  
Design Strategy ◽  
Nmr Studies ◽  
Cell Axis ◽  
Sequence Of Events ◽  
Concentrated Solution ◽  
Nuclear Overhauser ◽  
Nuclear Overhauser Effects ◽  
Hydrogen Bonded

Aniline–phenol recognition is studied in the crystal engineering context in several 1:1 cocrystals that contain a closed cyclic hydrogen-bonded [...O—H...N—H...]2tetramer supramolecular synthon (II). Twelve cocrystals of 3,4,5- and 2,3,4-trichlorophenol with one of eight halogenated anilines have been characterized. Ten of these cocrystals contain an extended octamer synthon that is assembled with hydrogen bonding and π...π stacking that defines aLong-Range Synthon Aufbau Module(LSAM). The design strategy is, therefore, based on the construction and transferability of the LSAM, which is a dimer of tetramers. Using the LSAM concept, two short cell axes in the crystal structures can be predicted. Whilst one of them is dictated by synthonII, the other one is dominated by π...π interactions. The third cell axis can also be predicted, in some cases, by systematic tuning of the halogen bonds. The design strategy is also verified in cocrystals of non-halogenated precursors. The observation of this large synthon in so many structures points to its stability and possible existence in solution. To this end, one-dimensional1H and15N NMR studies, performed on the 3,4,5-trichlorophenol–3,5-dichloroaniline cocrystal in CDCl3, show characteristic downfield shifts that point to a π...π stacked structure and to the robustness of the hydrogen-bonded aggregates. Nuclear Overhauser effects point to hydrogen bonding between aniline and phenol molecules in the aggregates. Diffusion-ordered spectroscopy andT1inversion recovery experiments show that stacking is present in concentrated solution and lost at a certain dilution. A sequence of events is therefore established: molecules of the aniline and the phenol associateviahydrogen bonding to form tetramers, and tetramers subsequently stack to form octamers.

Evaluation of the 2 NH2A—T Pair in Hybridization, I Synthesis of the DNA/RNA Hybrid Oligomers Containing 2-Aminoadenosines

1988 ◽  
Vol 43 (5) ◽  
pp. 623-630 ◽  
Author(s):  
Kaeko Kikuchi ◽  
Yoshio Taniyama ◽  
Ryuji Marumoto
Keyword(s):  
Hydrogen Bonding ◽  
Dna Structure ◽  
Dna Duplexes ◽  
Cd Spectra ◽  
Base Pairing ◽  
Base Stacking ◽  
Base Pairs ◽  
Nuclease P1 ◽  
Rna Duplexes

Abstract DNA decamers containing 2-aminoadenosine were synthesized. Oligonucleotide duplexes including the 2 NH2A-T base pairs were prepared and their Tm profile examined. Contrary to expectation, elevation of the Tm value by the 2 NH2 group is very small in DNA/RNA duplexes. From the CD spectra measurement, we assume that the distortion of the B-DNA structure caused by scattered DNA/RNA base pairing diminishes the efficient hydrogen bonding and base stacking of the duplexes. It was also found that the DNA duplexes containing 2-aminoadenosine hybrids are considerably resistant to ribonuclease T2 or nuclease P1 digestion.

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