Design and structure-based study of new potential FKBP12 inhibitors
文献类型：期刊论文
| 作者 | Sun, F; Li, PY; Ding, Y; Wang, LW; Bartlam, M; Shu, CL; Shen, BF; Jiang, HL ; Li, S; Rao, ZH
|
| 刊名 | BIOPHYSICAL JOURNAL
 |
| 出版日期 | 2003-11-01 |
| 卷号 | 85期号:5页码:3194-3201 |
| ISSN号 | 0006-3495 |
| DOI | 10.1016/S0006-3495(03)74737-7 |
| 文献子类 | Article |
| 英文摘要 | Based on the structure of FKBP12 complexed with FK506 or rapamycin, with computer-aided design, two neurotrophic ligands, (3R)-4-(p-Toluenesulfonyl)-1,4-thiazane-3-carboxylic acid-L-Leucine ethyl ester and (3R)-4-(p-Toluene-sulfonyl)-1,4-thiazane-3-carboxylic acid-L-phenylalanine benzyl ester, were designed and synthesized. Fluorescence experiments were used to detect the binding affinity between FKBP12 and these two ligands. Complex structures of FKBP12 with these two ligands were obtained by x-ray crystallography. In comparing FKBP12-rapamycin complex and FKBP12-FK506 complex as well as FKBP12-GPI-1046 solution structure with these new complexes, significant volume and surface area effects and obvious contact changes were detected which are expected to cause their different binding energies-showing these two novel ligands will become more effective neuron regeneration drugs than GPI-1046, which is currently undergoing phase II clinical trail as a neurotrophic drug. Analysis of volume and surface area effects also gives a new clue for structure-based drug design. |
| WOS关键词 | NEUROIMMUNOPHILIN LIGANDS ; FK506-BINDING PROTEIN ; IMMUNOPHILIN LIGANDS ; NEUROTROPHIC LIGAND ; FKBP-12 LIGANDS ; BINDING-PROTEIN ; CYCLOSPORINE-A ; CALCINEURIN ; COMPLEX ; FK506 |
| WOS研究方向 | Biophysics |
| 语种 | 英语 |
| WOS记录号 | WOS:000186190500038 |
| 出版者 | CELL PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/274158]  |
| 专题 | 新药研究国家重点实验室 中科院受体结构与功能重点实验室 |
| 通讯作者 | Li, S |
| 作者单位 | 1.Chinese Acad Sci, Natl Lab Biol Macromol, Beijing 100080, Peoples R China 2.Acad Mil Med Sci, Inst Pharmacol & Toxicol, Beijing, Peoples R China 3.Tsinghua Univ, Struct Biol Lab, Sch Life Sci & Engn, Beijing 100084, Peoples R China 4.Tsinghua Univ, Minist Educ, Lab Prot Sci, Beijing 100084, Peoples R China 5.Acad Mil Med Sci, Inst Basic Med Sci, Beijing, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Biol Sci, Drug Discovery & Design Ctr, State Key Lab Drug Res,Shanghai Inst Mat Med, Shanghai, Peoples R China 7.Chinese Acad Sci, Inst Biophys, Beijing 100080, Peoples R China |
| 推荐引用方式 GB/T 7714 | Sun, F,Li, PY,Ding, Y,et al. Design and structure-based study of new potential FKBP12 inhibitors[J]. BIOPHYSICAL JOURNAL,2003,85(5):3194-3201. |
| APA | Sun, F.,Li, PY.,Ding, Y.,Wang, LW.,Bartlam, M.,...&Rao, ZH.(2003).Design and structure-based study of new potential FKBP12 inhibitors.BIOPHYSICAL JOURNAL,85(5),3194-3201. |
| MLA | Sun, F,et al."Design and structure-based study of new potential FKBP12 inhibitors".BIOPHYSICAL JOURNAL 85.5(2003):3194-3201. |
入库方式： OAI收割
来源：上海药物研究所
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