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Binding to human serum albumin of zidovudine (AZT) and novel AZT derivatives. Experimental and theoretical analyses. 2008

Mario A Quevedo, and Sergio R Ribone, and Guillermo N Moroni, and Margarita C Briñón
Dpto. Farmacia, Fac. Ciencias Químicas-U.N.C., Córdoba, Argentina.

This work presents the binding of AZT and nine novel AZT derivatives to human serum albumin (HSA), both defatted (HSA(D)) and complexed with fatty acids (HSA(FA)). The bound fractions and binding site were determined by applying an ultrafiltration procedure, with an increased affinity for the majority of these derivatives to HSA(D) being found with respect to that of AZT, while only one derivative exhibited an increased affinity for HSA(FA). By means of computational methods, we observed that specific electrostatic interactions are responsible for the increased affinity for HSA(D), while the presence of fatty acids complexed to HSA caused an intense electrostatic repulsion with negatively charged ligands located in Sudlow site I, thus diminishing their bound fractions. A strong relationship between the calculated energetic components and the observed experimental affinity was identified.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
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
D005227 Fatty Acids Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed) Aliphatic Acid,Esterified Fatty Acid,Fatty Acid,Fatty Acids, Esterified,Fatty Acids, Saturated,Saturated Fatty Acid,Aliphatic Acids,Acid, Aliphatic,Acid, Esterified Fatty,Acid, Saturated Fatty,Esterified Fatty Acids,Fatty Acid, Esterified,Fatty Acid, Saturated,Saturated Fatty Acids
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D012709 Serum Albumin A major protein in the BLOOD. It is important in maintaining the colloidal osmotic pressure and transporting large organic molecules. Plasma Albumin,Albumin, Serum
D014462 Ultrafiltration The separation of particles from a suspension by passage through a filter with very fine pores. In ultrafiltration the separation is accomplished by convective transport; in DIALYSIS separation relies instead upon differential diffusion. Ultrafiltration occurs naturally and is a laboratory procedure. Artificial ultrafiltration of the blood is referred to as HEMOFILTRATION or HEMODIAFILTRATION (if combined with HEMODIALYSIS).
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
D055672 Static Electricity The accumulation of an electric charge on a object Electrostatic,Electrostatics,Static Charge,Charge, Static,Charges, Static,Electricity, Static,Static Charges

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