Cationic polyrotaxanes effectively inhibit uptake via carnitine/organic cationic transporters without cytotoxicity.
We examined the inhibitory effect of cationic polyrotaxanes, which consist of alpha-cyclodextrins threaded on a poly(ethylene glycol) (PEG) chain, on the activity of the intestinal carnitine/organic cation transporter, OCTN2, in OCTN2 gene-transfected HEK293/PDZK1 cells. The cationic polyrotaxanes effectively inhibited the OCTN2-mediated carnitine transport. Polyrotaxanes with a longer PEG chain exhibited a greater inhibitory effect, possibly owing to multivalent interactions with binding sites on OCTN2. These cationic polyrotaxanes were far less cytotoxic than conventional polycations, and are therefore interesting candidates as low-toxicity inhibitors of cation transport at cell surfaces.
Utsunomiya
Hideto
H
School of Materials Science, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi, Ishikawa 923-1292, Japan.
Katoono
Ryo
R
Yui
Nobuhiko
N
Sugiura
Tomoko
T
Kubo
Yoshiyuki
Y
Kato
Yukio
Y
Tsuji
Akira
A
D001692:Biological Transport / Q000187:drug effects; D002331:Carnitine / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D027701:Organic Cation Transport Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology*; D043862:Rotaxanes / Q000737:chemistry / Q000494:pharmacology*; D000074058:Solute Carrier Family 22 Member 5; D047391:alpha-Cyclodextrins / Q000737:chemistry / Q000494:pharmacology*
D027701:Organic Cation Transport Proteins; D043862:Rotaxanes; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D047391:alpha-Cyclodextrins; D011092:Polyethylene Glycols; D002331:Carnitine