Binding to Human Serum Albumin of AZT and Novel AZT Derivatives. Experimental and Theoretical Analyses

QUEVEDO, M.A.; RIBONE, S.R.; MORONI, G.N.; BRIÑÓN, M.C.

BIOORGANIC & MEDICINAL CHEMISTRY.

Elsevier

Año: 2008 vol. 16 p. 2779 - 2779

0968-0896

his 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.