3'-azido-3'-deoxythymidine binding to ribonuclease A: model for drug-protein interaction. 2003

S Gaudreau, and A Novetta-Dellen, and J F Neault, and S Diamantoglou, and H A Tajmir-Riahi
Department of Chemistry-Biology, University of Québec at Trois-Rivières, C.P. 500, Trois-Rivières, Québec G9A 5H7, Canada.

Ribonuclease A (RNase A) with several high affinity binding sites is a possible target for many organic and inorganic molecules. 3'-Azido-3'-deoxythymidine (AZT) is the first clinically effective drug for the treatment of human immunodeficiency virus (HIV) infection. The drug interactions with protein and nucleic acids are associated with its mechanism of action in vivo. This study was designed to examine the interaction of AZT with RNase A under physiological conditions. Reaction mixtures of constant protein concentration (2%) and different drug contents (0.0001-0.1 mM) are studied by UV-visible, FTIR, and circular dichroism spectroscopic methods in order to determine the drug binding mode, the drug binding constant, and the effects of drug complexation on the protein and AZT conformations in aqueous solution. The spectroscopic results showed one major binding for the AZT-RNase complexes with an overall binding constant of 5.29 x 10(5) M(-1). An increase in the protein alpha helicity was observed upon AZT interaction, whereas drug sugar pucker remained in the C2'-endo/anti conformation in the AZT-RNase complexes.

UI MeSH Term Description Entries
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D002417 Cattle Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor. Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D002942 Circular Dichroism A change from planar to elliptic polarization when an initially plane-polarized light wave traverses an optically active medium. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Circular Dichroism, Vibrational,Dichroism, Circular,Vibrational Circular Dichroism
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012259 Ribonuclease, Pancreatic An enzyme that catalyzes the endonucleolytic cleavage of pancreatic ribonucleic acids to 3'-phosphomono- and oligonucleotides ending in cytidylic or uridylic acids with 2',3'-cyclic phosphate intermediates. EC 3.1.27.5. RNase A,Ribonuclease A,Pancreatic RNase,RNase I,Ribonuclease (Pancreatic),Ribonuclease I,Pancreatic Ribonuclease,RNase, Pancreatic
D015215 Zidovudine A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. AZT (Antiviral),Azidothymidine,3'-Azido-2',3'-Dideoxythymidine,3'-Azido-3'-deoxythymidine,AZT Antiviral,AZT, Antiviral,BW A509U,BWA-509U,Retrovir,3' Azido 2',3' Dideoxythymidine,3' Azido 3' deoxythymidine,Antiviral AZT,BWA 509U,BWA509U
D017433 Protein Structure, Secondary The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to ALPHA-HELICES; BETA-STRANDS (which align to form BETA-SHEETS), or other types of coils. This is the first folding level of protein conformation. Secondary Protein Structure,Protein Structures, Secondary,Secondary Protein Structures,Structure, Secondary Protein,Structures, Secondary Protein
D017550 Spectroscopy, Fourier Transform Infrared A spectroscopic technique in which a range of wavelengths is presented simultaneously with an interferometer and the spectrum is mathematically derived from the pattern thus obtained. FTIR,Fourier Transform Infrared Spectroscopy,Spectroscopy, Infrared, Fourier Transform

Related Publications

S Gaudreau, and A Novetta-Dellen, and J F Neault, and S Diamantoglou, and H A Tajmir-Riahi
January 1992, Drug metabolism and disposition: the biological fate of chemicals,
S Gaudreau, and A Novetta-Dellen, and J F Neault, and S Diamantoglou, and H A Tajmir-Riahi
May 1994, The Journal of biological chemistry,
S Gaudreau, and A Novetta-Dellen, and J F Neault, and S Diamantoglou, and H A Tajmir-Riahi
April 1988, Acta crystallographica. Section C, Crystal structure communications,
S Gaudreau, and A Novetta-Dellen, and J F Neault, and S Diamantoglou, and H A Tajmir-Riahi
June 1997, Journal of virology,
S Gaudreau, and A Novetta-Dellen, and J F Neault, and S Diamantoglou, and H A Tajmir-Riahi
October 1994, Biochemical pharmacology,
S Gaudreau, and A Novetta-Dellen, and J F Neault, and S Diamantoglou, and H A Tajmir-Riahi
October 1990, Experimental hematology,
S Gaudreau, and A Novetta-Dellen, and J F Neault, and S Diamantoglou, and H A Tajmir-Riahi
January 1995, Pharmacotherapy,
S Gaudreau, and A Novetta-Dellen, and J F Neault, and S Diamantoglou, and H A Tajmir-Riahi
January 1991, Journal of virology,
S Gaudreau, and A Novetta-Dellen, and J F Neault, and S Diamantoglou, and H A Tajmir-Riahi
June 1995, Drug metabolism and disposition: the biological fate of chemicals,
S Gaudreau, and A Novetta-Dellen, and J F Neault, and S Diamantoglou, and H A Tajmir-Riahi
June 1989, Antimicrobial agents and chemotherapy,
Copied contents to your clipboard!