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Fluoroquinacrine binding to nucleic acids: Investigation of the 19 F‐nmr, optical, and fluorescence properties in the presence of DNA, poly(A), and tRNA
Author(s) -
Mirau P. A.,
Shafer R. H.,
James T. L.,
Bolton P. H.
Publication year - 1982
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360210505
Subject(s) - nucleic acid , chemistry , absorbance , dna , fluorescence , nuclear magnetic resonance spectroscopy of nucleic acids , nuclear magnetic resonance spectroscopy , transfer rna , base pair , proton nmr , stereochemistry , crystallography , rna , biochemistry , fluorine 19 nmr , transverse relaxation optimized spectroscopy , chromatography , physics , quantum mechanics , gene
The interaction of fluoroquinacrine, 3‐fluoro‐7‐chloro‐9‐(diethylamino‐1‐methylbutyl‐amino)acridine, with poly(A), DNA, and tRNA has been investigated by monitoring changes in the 19 F‐nmr properties, the fluorescence, and the optical absorbance of the drug. The changes in the properties of fluoroquinacrine in the presence of nucleic acids are similar to those observed for quinacrine and suggest that the drugs bind in a similar fashion. The molecular dynamics of fluoroquinacrine bound to nucleic acids were determined by interpreting the data from a number of different nmr relaxation experiments with a two‐correlation‐time model. The two motions are the long‐range bending motion of the drug‐nucleic acid complex and the sliding of the drug between the base pairs. Both dipolar and chemical shift anisotropy contributions to the nmr relaxation parameters were taken into consideration. The binding of fluoroquinacrine to tRNA appears to be different from that observed for binding to DNA. Optical absorbance and 19 F‐nmr were also used to examine the helix‐to‐coil transitions of the drug–nucleic acid complexes. In the DNA complex, the 19 F chemical shift changes parallel the absorption changes that occur during the transition. 19 F‐nmr and absorption show that the drug–tRNA complexes undergo a cooperative helix‐to‐coil transition, with the drug binding sites melting when the tRNA is 70% denatured.