2005 Fiscal Year Final Research Report Summary
Design of supramolecular ligands that can multivalently interact with receptor proteins on cellular membranes
| Project/Area Number |
14380397
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Biomedical engineering/Biological material science
|
|---|
| Research Institution | Japan Advanced Institute of Science and Technology |
|---|
Principal Investigator |
YUI Nobuhiko Japan Advanced Institute of Science and Technology, School of Materials Science, Professor, 材料科学研究科, 教授 (70182665)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
OOYA Tooru Japan Advanced Institute of Science and Technology, School of Matirials Science, Associate, 材料科学研究科, 助手 (10301201)
|
|---|
| Project Period (FY) |
2002 – 2005
|
| Keywords | Polyrotaxane / Cyclodextrins / Poly(ethylene glycol) / Supramolecular / Sccharides / Gene / Gene expression / Biomaterials |
|---|
| Research Abstract |
In this research, new biomaterials using a polyrotaxane was designed and examined to achieve strong binding with receptor proteins on cellular membranes. The most definitive feature in polyrotaxanes, in which many cyclic compounds are threaded onto linear polymeric chains capped with bulky end-groups, is the noncovalent bonds between the cyclic compounds and the polymeric chain. Through the research, we found and clarified the following matters.
Multivalent Molecular Recognition Based on Sliding Motion of Saccharide-Polyrotaxane Conjugates : Saccharide, one of the ligands for targeting, in saccharide-polyrotaxane conjugates could easily diffuse in buffers via sliding and rotational motion of α-cyclodextrins (α-CDs) along a poly(ethylene glycol) (PEG) chain. A maltose-polyrotaxane conjugate with appropriate threading number of α-CDs exhibits high mobility of maltose in aqueous conditions. A high mobility of saccharide groups and α-Cds was proved by spin-lattice relaxation time (T_1) and
… More
spin-spin relaxation time (T_2) analysis. The association constant (K_a) between the conjugate and Concanavalin A (Con A) was in the range of 6 powers. The features of high mobility of the ligands and preserving the water clusters led to gaining a large negative enthalpy.
Erosion Time-Controllable Hydrogels Using Polyrotaxanes for Cartilege Tissue Enginnering : Hydrolyzable polyrotaxanes were utilized as a cross-linker for preparing PEG-polyrotaxane hydrogels (PEG-PRX gels) for biomedical applications. The hydrolysis of our designed PEG-PRX gels was found to well controlled by inclusion complexation of ester groups located at the terminal of the PEG in the polyrotaxanes, and the time to complete hydrogel erosion varies from a few days to more than a half year in spite of their highly swollen states in physiological conditions. By using the degradation control, the PEG-PRX gels could be designed as scaffolds for cartilege cultivation.
Plasmid DNA Delivery to Nucleus Based on Supramolecular Characteristics of Biocleavable Polyrotaxane : A biocleavable polyrotaxane, having a necklace-like structure consisting of many cationic α-CDs and a disulfide-introduced PEG, was examined as a non-viral gene carrier. The polyrotaxane formed a stable polyplex having positively charged surface even at low charge ratio. The pDNA decondensation occurred through disulfide cleavage of the polyrotaxane and subsequent supramolecular dissociation of the non-covalent linkages between α-CDs and PEG. Rapid endosomal escape was observed, and the transfection of the DMAE-SS-PRX polyplex is independent of the amount of free polycation. Those properties played a key role for delivery of pDNA clusters to nucleus Less
|
-
-
[Journal Article] Biocleavable Polyrotaxane - Plasmid DNA Polyplex for Enhanced Gene Delivery2006
Author(s)
Ooya, T, Choi, H.S, Yamashita, A, Yui, N, Sugaya, Y, Kano, A, Akita, H, Kogure, K, Ito, R, Harashima,H.
-
Journal Title
J.Am.Chem.Soc. 128
Pages: 3582-3583
Description
「研究成果報告書概要(和文)」より
-
-
[Journal Article] Biocleavable Polyrotaxane - Plasmid DNA Polyplex for Enhanced Gene Delivery2006
Author(s)
Ooya, T, Choi, H.S, Yamashita, A, Yui, N, Sugaya, Y, Kano, A, Akita, H, Kogure, K, Ito, R, Harashima, H.
-
Journal Title
J.Am.Chem.Soc. 128
Pages: 3582-3583
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-
-
-
