tRNA binding to antitumor drug doxorubicin and its analogue

The binding sites of antitumor drug doxorubicin (DOX) and its analogue N-(trifluoroacetyl) doxorubicin (FDOX) with tRNA were located, using FTIR, CD, fluorescence spectroscopic methods and molecular modeling. Different binding sites are involved in drug-tRNA adducts with DOX located in the vicinity...

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Bibliographic Details
Published in:PloS one 2013-07, Vol.8 (7), p.e69248-e69248
Main Authors: Agudelo, Daniel, Bourassa, Philippe, Beauregard, Marc, Bérubé, Gervais, Tajmir-Riahi, Heidar-Ali
Format: Article
Language:English
Subjects:
Adducts
Analogue
Antibiotics
Antineoplastic Agents - chemistry
Antineoplastic Agents - metabolism
Binding sites
Biology
Biopolymers
Chemistry
Circular Dichroism
Conformation
Deoxyribonucleic acid
DNA
Doxorubicin
Doxorubicin - analogs & derivatives
Doxorubicin - chemistry
Doxorubicin - metabolism
Drug Stability
Fluorescence
Fourier transforms
Hydrogen-Ion Concentration
Hydrophobicity
Kinetics
Medicine
Molecular Docking Simulation
Molecular modelling
Nucleic Acid Conformation
Particle formation
Physics
Proteins
Ribonucleotides - chemistry
RNA Stability
RNA, Transfer - chemistry
RNA, Transfer - metabolism
Solutions
Spectrometry, Fluorescence
Spectroscopy
Spectroscopy, Fourier Transform Infrared
Thermodynamics
Trifluoroacetyl
tRNA
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Summary:The binding sites of antitumor drug doxorubicin (DOX) and its analogue N-(trifluoroacetyl) doxorubicin (FDOX) with tRNA were located, using FTIR, CD, fluorescence spectroscopic methods and molecular modeling. Different binding sites are involved in drug-tRNA adducts with DOX located in the vicinity of A-29, A-31, A-38, C-25, C-27, C-28, G-30 and U-41, while FDOX bindings involved A-23, A-44, C-25, C-27, G-24, G-42, G-53, G-45 and U-41 with similar free binding energy (-4.44 for DOX and -4.41 kcal/mol for FDOX adducts). Spectroscopic results showed that both hydrophilic and hydrophobic contacts are involved in drug-tRNA complexation and FDOX forms more stable complexes than DOX with K DOX-tRNA=4.7 (± 0.5)× 10(4) M(-1) and K FDOX-tRNA=6.3 (± 0.7)× 10(4) M(-1). The number of drug molecules bound per tRNA (n) was 0.6 for DOX and 0.4 for FDOX. No major alterations of tRNA structure were observed and tRNA remained in A-family conformation, while biopolymer aggregation and particle formation occurred at high drug concentrations.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0069248