2006 Fiscal Year Final Research Report Summary
Drug Design for mutant Vitamin D receptor
| Project/Area Number |
17590100
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Drug development chemistry
|
|---|
| Research Institution | National Institute of Health Sciences |
|---|
Principal Investigator |
KURIHARA Masaaki National Institute of Health Sciences, Section chief, 有機化学部, 室長 (20205206)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Keywords | vitamin D_3 analogues / vitamin D receptor / hereditary vitamin D-resistant rickets / docking study / ノンセコ型リガンド |
|---|
| Research Abstract |
Vitamin D receptor (VDR) belongs to the steroid/thyroid hormone nuclear receptor superfamily. The X-ray crystal structure of the ligand binding domain (LBD) of VDR with 1α,25-dihydroxyvitamin D_3 was determined by Moras et al. in 2000 and the binding mode between ligands and LBD-VDR was revealed.
Hereditary vitamin D-resistant rickets (HVDRR) is a genetic disorder caused by mutations in the vitamin D receptor, which lead to resistance to 1α,25-dihydroxyvitamin D_3 [1α,25(OH)_2D_3]. We found that the A ring-modified analogues, 2α-(3-hydroxypropyl)-and 2α-(3-hydroxypropoxy)-1α,25(OH)_2D_3, (O1C3 and O2C3) can bind better than the natural hormone to the mutant VDR (R274A), which similar to the HVDRR mutant, R274L, had lost the hydrogen bond to the 1α-hydroxyl group of 1α,25(OH)_2D_3. We have also studied on docking models.
|
Research Products
(13 results)
-
-
-
-
-
-
-
-
-
[Journal Article] Design, Synthesis and Biological Evaluation of Novel 1 α,25-Dihydroxyvitamin D3 Analogues Possessing Aromatic Ring on 2α-Position2005
Author(s)
S.Honzawa, K.Hirasaka, Y.Yamamoto, S, Peleg, T, Fujishima, M.Kurihara, N.Saito, S.Kishimoto, T.Sugiura, K.Waku, H.Takayama, A.Kittaka
-
Journal Title
Tetrahedron 61
Pages: 11253-11263
Description
「研究成果報告書概要(欧文)」より
-
-
[Journal Article] Computational Study on Conformation of Oligopeptides Containing Chiral Cyclic α,α-Disubstituted α-Amino Acids2005
Author(s)
M.Kurihara, Y.Sato, W.Hakamata, H.Okuda, Y.Demizu, M.Nagano, N.Kawabe, M.Doi, M.Tanaka, H.Suemune
-
Journal Title
Peptide Science (2006)
Pages: 371-372
Description
「研究成果報告書概要(欧文)」より
-
-
