title: Inhibitory effect of supramolecular polyrotaxane-dipeptide conjugates on digested peptide uptake via intestinal human peptide transporter.
abstract: The effect of polyrotaxane-dipeptide (Val-Lys) conjugates on the uptake of a model dipeptide (Gly-Sar) was examined via human peptide transporter (hPEPT1) on HeLa cells. Here, Val-Lys groups are introduced to alpha-CDs, which are threaded onto a poly(ethylene oxide) chain capped with bulky end-groups (polyrotaxane). The Gly-Sar uptake via hPEPT1 was significantly inhibited in the polyrotaxane conjugates, and this inhibitory effect was not explained by the sum of interaction between hPEPT1 and alpha-CD-Val-Lys conjugates. Further, the inhibition was significantly greater than those observed in dextran-Val-Lys conjugates. Therefore, our data clearly suggests that supramolecular structure in the polyrotaxane conjugates contributes considerably to the inhibitory effect via multivalent binding of Val-Lys groups with hPEPT1.
authors: School of Materials Science, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Tatsunokuchi, Ishikawa 923-1292, Japan. yui@jaist.ac.jp
authors: Nobuhiko
authors: N
authors: Yui
authors: Tooru
authors: T
authors: Ooya
authors: Tomokatsu
authors: T
authors: Kawashima
authors: Yoshimasa
authors: Y
authors: Saito
authors: Ikumi
authors: I
authors: Tamai
authors: Yoshimichi
authors: Y
authors: Sai
authors: Akira
authors: A
authors: Tsuji
mesh_terms: D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D003505:Cyclodextrins / Q000737:chemistry / Q000378:metabolism; D004151:Dipeptides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000737:chemistry; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010446:Peptide Fragments / Q000378:metabolism; D000074011:Peptide Transporter 1; D011083:Polycyclic Compounds / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D043862:Rotaxanes; D027981:Symporters
chemical_list: D002352:Carrier Proteins; D003505:Cyclodextrins; D004151:Dipeptides; D005456:Fluorescent Dyes; D010446:Peptide Fragments; D000074011:Peptide Transporter 1; D011083:Polycyclic Compounds; D043862:Rotaxanes; C082186:SLC15A1 protein, human; D027981:Symporters; C074992:valyllysine; C004194:glycylsarcosine; D011092:Polyethylene Glycols