Effects of cell-permeating peptide binding on the distribution of 125I-labeled Fab fragment in rats.
The peptides comprising the sequence of HIV-1 Tat protein (positions 48-60), Antennapedia (positions 43-58), and HIV-1 Rev protein (positions 34-50) are known to be cell-permeating. In this study, we examined how the distribution of Fab fragments in rats is affected by conjugation with these peptides. Fab fragment was iodinated by a chloramine-T method and then chemically conjugated with cell-permeating peptide. The complex of 125I-Fab and cell-permeating peptide was administered to male rats intravenously at a dose of 1 mg/kg, and whole-body autoradiography was performed at 4 and 24 h after administration. The patterns of distribution of 125I-Fab exhibited remarkable variation depending on the cell-permeating peptide used. In particular, at 4 h, high concentrations of radioactivity were observed in the spleen, adrenal gland, renal medulla, and liver with Rev peptide-Fab complex, in the liver and spleen with Tat peptide-Fab complex, and in the spleen, adrenal gland, and liver with Antennapedia peptide-Fab complex. Even at 24 h, high concentrations of radioactivity were still observed in the spleen and renal medulla of rat with Rev peptide-Fab complex, and in the spleen and renal cortex of rat with Antennapedia peptide-Fab complex. These findings demonstrate that the patterns of distribution of peptide-125I-Fab complexes can be modulated by selection of cell-penetrating peptides. Moreover, the patterns of retention of peptide-125I-Fab complexes in internal organs also differed at 24 h after administration. These findings provide valuable information for the development of novel antibody pharmaceuticals and therapeutic systems.
Kameyama
Shouju
S
Research Planning, Bipha Corporation, Chitose, Hokkaido 066-0051, Japan. Kameyama.Shouju@mm.m-pharma.co.jp
Horie
Mayo
M
Kikuchi
Takeo
T
Omura
Takao
T
Takeuchi
Toshihide
T
Nakase
Ikuhiko
I
Sugiura
Yukio
Y
Futaki
Shiroh
S
D000595:Amino Acid Sequence; D000818:Animals; D001345:Autoradiography; D002463:Cell Membrane Permeability / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000032:analysis* / Q000097:blood / Q000737:chemistry*; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D051381:Rats
D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes; D010455:Peptides