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  • 1
    ISSN: 1573-5001
    Schlagwort(e): A ⋅ (G ⋅ G ⋅ G ⋅ G) ⋅ A hexad ; G ⋅ C ⋅ G ⋅ C tetrad ; G ⋅ G ⋅ G ⋅ G tetrad ; HNN-COSY ; 2hJNN
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract Several structural motifs found in nucleic acids involve N-H ... N hydrogen bonds in which the donor hydrogens are broadened to extinction due to chemical or conformational exchange. In such situations, it is impossible to use the well-established HNN-COSY or soft HNN-COSY experiments, which report the presence of the hydrogen bond directly on the donor proton(s). We present a pulse sequence, H(CN)N(H), for alleviating this problem in hydrogen bonds of the type NdH ... Na-CH, in which the donor Nd nitrogen is correlated with the corresponding non-exchangeable C-H proton associated with the acceptor Na nitrogen. In this way, missing NdH ... Na correlations in an HNN-COSY spectrum may be recovered from CH-Nd correlations in the H(CN)N(H) spectrum. By correlating a different set of nuclei relative to the HNN-COSY class of experiments, the H(CN)N(H) experiment also serves to remove ambiguities associated with degeneracies in HNN-COSY spectra. The technique is demonstrated on d(GGAGGAG)4,a quadruplex containing a novel A ⋅ (G ⋅ G ⋅ G ⋅ G) ⋅ A hexad and on d(GGGCAGGT)4, containing a G ⋅ C ⋅ G ⋅ C tetrad, in which missing NH2 ... N7 correlations are retrieved via H8-(N2,N6) correlations in the H(CN)N(H) spectrum.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Journal of biomolecular NMR 1 (1991), S. 323-347 
    ISSN: 1573-5001
    Schlagwort(e): Drug-DNA interaction ; Actinomycin ; Restrained molecular dynamics ; Nuclear Overhauser effect ; NOE ; 2D NMR
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Summary The actinomycin-D-d(A1-A2-A3-G4-C5-T6-T7-T8) complex (1 drug per duplex) has been generated in aqueous solution and its structure characterized by a combined application of two-dimensional NMR experiments and molecular dynamics calculations. We have assigned the exchangeable and nonexchangeable proton resonances of Act and d(A3GCT3) in the complex and identified the intermolecular proton-proton NOES that define the alignment of the antitumor agent at its binding site on duplex DNA. The molecular dynamics calculations were guided by 70 intermolecular distance constraints between Act and nucleic acid protons in the complex. The phenoxazone chromophore of Act intercalates at the (G-C)I·(G-C)II step in the d(A3GCT3) duplex with the phenoxazone ring stacking selectively with the G4I and G4II purine bases but not with C4I and C4II pyrimidine bases at the intercalation site. There is a pronounced unwinding between the A3·T6 and G4·C5 base pairs which are the next steps located in either direction from the intercalation site in the Act-d(A3GCT3) complex. The Act cyclic pentapeptide ring conformations in the complex are similar to those for free Act in the crystal except for a change in orientation of the ester linkage connecting meVal and Thr residues. The cyclic pentapeptide rings are positioned in the minor groove with the established G-C sequence specificity of binding associated with intermolecular hydrogen bonds between the Thr backbone CO and NH groups to the NH2-2 and N3 positions of guanosine, respectively. Complex formation is also stabilized by van der Waals interactions between nonpolar groups on the cyclic pentapeptide rings and the sugar residues and base pair edges lining the widened minor groove of the (A3-G4-C5-T6)I·(A3-G4-C5-T6)II binding site segment of the DNA helix.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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