Early Absorption and Distribution Analysis of Antitumor and Anti-AIDS Drugs:  Lipid Membrane and Plasma Protein Interactions

Abstract

The interactions of a set of compounds of potential importance for anticancer and AIDS chemotherapy with lipid membranes and plasma proteins were studied with a surface plasmon resonance (SPR) based optical biosensor, giving valuable information on the absorption and distribution of the compounds. The technique allowed both effective screening of compounds and more detailed kinetic and mechanistic analysis of specific interactions. The interaction with two different types of lipid membranes could be reliably measured at a drug concentration as low as 20 microM, allowing analysis of poorly soluble compounds. Distribution was evaluated by investigation of the interactions with two human plasma proteins, human serum albumin (HSA) and alpha(1)-acid glycoprotein (AGP). Two apparent binding sites were clearly defined for HSA: one with rapid and one with slow association and dissociation rates. The sites appear to differ in accessibility and recognition characteristics rather than in their capacities to form strong complexes with drugs.

Survey of the year 2005 commercial optical biosensor literature

“…Also, among the 881 articles describing Biacore-based studies, 84% included information about which platform was used: most often studies were performed using the 3000 (38%), 2000 (22%), X (16%), and 1000 (4%) platforms, with the residual 4% using S51 [157,757,760,761,768,[779][780][781][782][783][789][790][791]798,918], Flexchip (formerly Applied Biosystems 8500 Affinity Analyzer) [138,338,434,435,583], Q [926,928,929,931,933,934,936,939,940], J [199,240,614,827,915], and Bialite [873].…”

Species‐dependent stereoselective drug binding to albumin: A circular dichroism study

“…[23][24][25] This study used CD (circular dichroism) spectroscopy not only to determine the affinity constants of selected ligands to albumins from different species, but also to gain information on the stereochemistry of the bound drug. CD is well suited to monitoring the signal associated with the formation of the drug/protein complex, yielding direct information on the binding interaction without interfering with the equilibrium process.…”

Drug binding to human serum albumin: Abridged review of results obtained with high‐performance liquid chromatography and circular dichroism

“…This methodology results particularly promising for their potential application in drug protein binding screening and in kinetics investigations. [22][23][24][25][26] The present review essentially focuses on the application of the use of both immobilized albumin (biochromatography) and CD on the same protein-drug system in solution, largely on the basis of our previous publications. These methodologies have been shown to be efficient in characterizing the binding sites on the protein and to give evidence of the changes in the binding properties of the protein arising by interaction between different ligands.…”

“…This methodology is well suited for screening assay, because of the miniaturization of the system and the short time for the analysis that facilitates its automatization. [22][23][24][25][26] Moreover, with optical biosensors, neither of the interacting molecules needs to be labeled, and the response obtained is directly proportional to the mass of the analyte that binds to the surface. Therefore, the ligand binding interaction occurs in a condition as close as possible to its native state.…”