Structural and ligand-binding properties of serum albumin species interacting with a biomembrane interface.
In the process of drug development, preclinical testing using experimental animals is an important aspect, for verification of the efficacy and safety of a drug. Serum albumin is a major binding protein for endogenous and exogenous ligands and regulates their distribution in various tissues. In this study, the structural and drug-binding properties of albumins on a biomembrane surface were investigated using reverse micelles as a model membrane. In reverse micelles, the secondary structures of all albumins were found, to varying degrees, to be intermediate between the native and denatured states. The tertiary structures of human and bovine albumin were similar to those of the native and intermediate states, respectively, whereas those of the dog, rabbit, and rat were in a denatured state. Thus, bovine albumin is an appropriate model for studying structural changes in human albumin in a membrane-water phase. Binding studies also showed the presence of species difference in the change in binding capacity of albumins during their interaction with reverse micelles. Among the albumins, rat albumin appears to be a good model for the protein-mediated drug uptake of human albumin in a biomembrane environment. These findings are significant in terms of the appropriate extrapolation of pharmacokinetics and pharmacodynamics data in various animals to humans.
Kosa
Takamitsu
T
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
Nishi
Koji
K
Maruyama
Toru
T
Sakai
Norifumi
N
Yonemura
Naoko
N
Watanabe
Hiroshi
H
Suenaga
Ayaka
A
Otagiri
Masaki
M
D000818:Animals; D002942:Circular Dichroism; D003619:Dansyl Compounds / Q000737:chemistry / Q000378:metabolism; D004285:Dogs; D006801:Humans; D008024:Ligands; D008566:Membranes / Q000737:chemistry / Q000378:metabolism; D008823:Micelles; D010113:Oxyphenbutazone / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D012521:Sarcosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism*; D013045:Species Specificity; D013050:Spectrometry, Fluorescence
D003619:Dansyl Compounds; D008024:Ligands; D008823:Micelles; D012709:Serum Albumin; C037087:dansylsarcosine; D010113:Oxyphenbutazone; D012521:Sarcosine