The solution structure of the complex between 4',6-diamidino-2-phenylindole (DAPI) and DNA oligomer (d(CGATCG))(2) at a 2:1 drug/duplex ratio has been characterized by combined use of proton one- and two-dimensional NMR spectroscopy, molecular mechanics, and molecular dynamics computations. Intermolecular nuclear Overhauser effects (NOEs), DNA structure perturbations, and resonance shifts induced by binding provide evidence that DAPI interacts with DNA hexamer by two different binding mechanisms, in fast exchange on the NMR. time scale, without any significant distortion of the B-type conformation of DNA hexamer, The results indicate that the ligand binds into the minor groove of the central 5'-ATC-3' region of the hexamer and on the outside of the oligomer by a pi pi-stacking interaction with the terminal C1:G6 base pairs, A model for both binding mechanisms that accounts for all experimental data was generated by molecular mechanics and dynamics calculations based on experimental NOEs, In the minor groove binding, N2 amino group of G2 precludes a deep insertion of phenyl ring of DAPI into the groove, Position and orientation of the drug in the external stacking interaction resemble those suggested for intercalation of DAPI between C:G base pairs.

Trotta, E., D'Ambrosio, E., Ravagnan, G., Paci, M. (1996). Simultaneous and different binding mechanisms of 4',6-diamidino-2- phenylindole to DNA hexamer (d(CGATCG))2: A 1H NMR study. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 271(44), 27608-27614 [10.1074/jbc.271.44.27608].

Simultaneous and different binding mechanisms of 4',6-diamidino-2- phenylindole to DNA hexamer (d(CGATCG))2: A 1H NMR study

PACI, MAURIZIO
1996-01-01

Abstract

The solution structure of the complex between 4',6-diamidino-2-phenylindole (DAPI) and DNA oligomer (d(CGATCG))(2) at a 2:1 drug/duplex ratio has been characterized by combined use of proton one- and two-dimensional NMR spectroscopy, molecular mechanics, and molecular dynamics computations. Intermolecular nuclear Overhauser effects (NOEs), DNA structure perturbations, and resonance shifts induced by binding provide evidence that DAPI interacts with DNA hexamer by two different binding mechanisms, in fast exchange on the NMR. time scale, without any significant distortion of the B-type conformation of DNA hexamer, The results indicate that the ligand binds into the minor groove of the central 5'-ATC-3' region of the hexamer and on the outside of the oligomer by a pi pi-stacking interaction with the terminal C1:G6 base pairs, A model for both binding mechanisms that accounts for all experimental data was generated by molecular mechanics and dynamics calculations based on experimental NOEs, In the minor groove binding, N2 amino group of G2 precludes a deep insertion of phenyl ring of DAPI into the groove, Position and orientation of the drug in the external stacking interaction resemble those suggested for intercalation of DAPI between C:G base pairs.
1996
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/10 - BIOCHIMICA
English
Con Impact Factor ISI
4',6 diamidino 2 phenylindole; cytosine; dna; guanine; article; base pairing; dna conformation; dna sequence; drug dna binding; ligand binding; molecular dynamics; molecular model; nuclear overhauser effect; priority journal; proton nuclear magnetic resonance; Base Composition; Base Sequence; DNA; Indoles; Intercalating Agents; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Conformation; Molecular Structure; Nucleic Acid Conformation; Oligodeoxyribonucleotides
Trotta, E., D'Ambrosio, E., Ravagnan, G., Paci, M. (1996). Simultaneous and different binding mechanisms of 4',6-diamidino-2- phenylindole to DNA hexamer (d(CGATCG))2: A 1H NMR study. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 271(44), 27608-27614 [10.1074/jbc.271.44.27608].
Trotta, E; D'Ambrosio, E; Ravagnan, G; Paci, M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/44473
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