Multivalent interactions between biotin-polyrotaxane conjugates and streptavidin as a model of new targeting for transporters.
Kinetic analysis of interactions between biotin-polyrotaxane or biotin-alpha-cyclodextrin (biotin-alpha-CD) conjugates and streptavidin was carried out as a model of new targeting to transporters using the surface plasmon resonance (SPR) technique. The biotin-polyrotaxane conjugates, in which biotin-introduced alpha-CDs are threaded onto a poly(ethylene oxide) chain capped with bulky end-groups, are expected to increase the valency of biotin from monovalent to multivalent binding. The number of biotins conjugated with one polyrotaxane molecule varied from 11 to 78, and apparently increased the association equilibrium constant (K(a)), assuming pseudo-first-order kinetics. A detailed dissociation kinetics was analyzed and the re-binding of the biotin-polyrotaxane conjugates was observed on the streptavidin-deposited SPR surface. The magnitude of the re-binding is likely to become larger with increasing the number of biotins, suggesting multivalent interaction on the SPR surface. To quantify the effect of valency, competitive inhibition assay was performed in terms of the supramolecular structure of the polyrotaxane. The inhibitory potency of the biotin-polyrotaxane conjugate was found to be 4-5 times greater than that of the biotin-alpha-CD conjugate. Therefore, the biotin-polyrotaxane conjugates by supramolecular formation of the biotin-alpha-CD conjugate significantly switches from monovalent to multivalent bindings to the model binding protein, streptavidin.
Ooya
Tooru
T
School of Materials Science, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Tatsunokuchi, Ishikawa 923-1292, Japan.
Yui
Nobuhiko
N
D001710:Biotin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D004347:Drug Interactions; D007202:Indicators and Reagents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008956:Models, Chemical; D043862:Rotaxanes; D019809:Streptavidin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*
D007202:Indicators and Reagents; D026901:Membrane Transport Proteins; D043862:Rotaxanes; D001710:Biotin; D019809:Streptavidin