Binding to human serum albumin of zidovudine (AZT) and novel AZT derivatives. Experimental and theoretical analyses.
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.
Quevedo
Mario A
MA
Dpto. Farmacia, Fac. Ciencias Químicas-U.N.C., Córdoba, Argentina.
Ribone
Sergio R
SR
Moroni
Guillermo N
GN
Briñón
Margarita C
MC
D001665:Binding Sites; D005227:Fatty Acids; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*; D055672:Static Electricity; D014462:Ultrafiltration; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D005227:Fatty Acids; D012709:Serum Albumin; D015215:Zidovudine