Biosensor analysis of the interaction between immobilized human serum albumin and drug compounds for prediction of human serum albumin binding levels.
The interactions between a set of drugs, selected on the basis of reported human serum albumin (HSA) binding levels, and immobilized HSA were investigated using surface plasmon resonance technology. Major HSA binding sites were available after immobilization. The intensity of the signal obtained from the interaction of the drug with the HSA surface was correlated with the reported HSA binding level. Drugs were classified into groups corresponding to high, medium, or low HSA binding based on the injection of the drug at 80 microM concentration. A set of 10 drugs binding to alpha(1)-acid glycoprotein (AGP) was also investigated and correlated with reported AGP binding data. The throughput of the presented assay is 100 compounds/24 h, and the sample consumption is less than 100 microL (8 nmol).
Frostell-Karlsson
A
A
Biacore AB, Rapsgatan 7, S-754 50 Uppsala, Sweden. asa.frostellkarlsson@biacore.com
Remaeus
A
A
Roos
H
H
Andersson
K
K
Borg
P
P
Hämäläinen
M
M
Karlsson
R
R
D001665:Binding Sites; D015374:Biosensing Techniques; D004074:Digitoxin / Q000378:metabolism; D004355:Drug Stability; D006801:Humans; D008970:Molecular Weight; D009288:Naproxen / Q000378:metabolism; D009961:Orosomucoid / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011485:Protein Binding; D011803:Quinine / Q000378:metabolism; D012293:Rifampin / Q000378:metabolism; D019438:Ritonavir / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism*; D012997:Solvents; D014859:Warfarin / Q000378:metabolism
D009961:Orosomucoid; D004364:Pharmaceutical Preparations; D012709:Serum Albumin; D012997:Solvents; D009288:Naproxen; D014859:Warfarin; D011803:Quinine; D004074:Digitoxin; D019438:Ritonavir; D012293:Rifampin