Early absorption and distribution analysis of antitumor and anti-AIDS drugs: lipid membrane and plasma protein interactions.
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.
Cimitan
Samanta
S
Department of Biochemistry, Uppsala University, Box 576, SE-751 23 Uppsala, Sweden.
Lindgren
Maria T
MT
Bertucci
Carlo
C
Danielson
U Helena
UH
D000042:Absorption; D019380:Anti-HIV Agents / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry*; D001665:Binding Sites; D015374:Biosensing Techniques; D001798:Blood Proteins / Q000737:chemistry*; D016333:HIV Protease / Q000737:chemistry; D017320:HIV Protease Inhibitors / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008055:Lipids / Q000737:chemistry*; D008567:Membranes, Artificial; D009961:Orosomucoid / Q000737:chemistry; D012709:Serum Albumin / Q000737:chemistry; D020349:Surface Plasmon Resonance; D043823:Taxoids / Q000737:chemistry
D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D001798:Blood Proteins; D017320:HIV Protease Inhibitors; D008055:Lipids; D008567:Membranes, Artificial; D009961:Orosomucoid; D012709:Serum Albumin; D043823:Taxoids; D016333:HIV Protease