ZIB

Hits per page

hits 1 - 2 | 2 hits

Sorting

Electronic Resource

Solution structure of actinomycin-DNA complexes: Drug intercalation at isolated G-C sites (1991)

Liu, Xiucai ; Chen, Huifen ; Patel, Dinshaw J.

Springer

Journal of biomolecular NMR 1 (1991), S. 323-347

add to mindlist on the mindlist

Details

ISSN: 1573-5001

Keywords: Drug-DNA interaction ; Actinomycin ; Restrained molecular dynamics ; Nuclear Overhauser effect ; NOE ; 2D NMR

Source: Springer Online Journal Archives 1860-2000

Topics: Biology , Chemistry and Pharmacology

Notes: 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.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF02192858

Permalink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Paper (German National Licenses)

Fulltext

Electronic Resource

Heteronuclear two-dimensional 15N- and 13C-nmr studies of DNA oligomers and their netropsin complexes using indirect proton detection (1991)

Ashcroft, Joseph ; Live, David H. ; Patel, Dinshaw J. ; [et al.]

New York : Wiley-Blackwell

Biopolymers 31 (1991), S. 45-55

add to mindlist on the mindlist

Details

ISSN: 0006-3525

Keywords: Chemistry ; Polymer and Materials Science

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Chemistry and Pharmacology

Notes: Heteronuclear multispin coherence proton-detected two-dimensional nmr spectroscopic experiments were used to obtain information on protonated carbons and nitrogens of the self-complementary d (G-G-T-A-T-A-C-C) and d (G-G-A-A-T-T-C-C) duplexes, with and without the drug netropsin dissolved in aqueous solution. Many correlations of protons coupled to 13C nuclei on the base and sugar rings of the octanucleotides were detected, allowing the carbon resonances to be assigned based on previous homonuclear proton two-dimensional nmr studies. Imino nitrogen assignments can also be made using the proton assignments from previous one-dimensional nuclear overhauser effect experiments. Imino nitrogen shifts may be useful indicators of changes in local hydrogen-bonding interactions to base-pair edges.

Additional Material: 6 Ill.