|
OALib Journal期刊
ISSN: 2333-9721
费用：99美元
|
|
|
|
以hif-1α和p300相互作用为靶点的抑制剂筛选模型的建立
, PP. 849-853
Keywords: 缺氧诱导因子1-α,p300,相互作用,哺乳动物双杂交,筛选
Abstract:
本研究以hif-1α和p300的相互作用为靶点，设计并构建了基于哺乳动物双杂交体系的hif-1特异性抑制剂筛选方法。通过克隆hif-1α和p300相互作用的基因序列，成功构建重组质粒pbind-hif1α和pact-p300，进而在hek293细胞中验证了hif-1α和p300蛋白在哺乳动物双杂交体系中确实存在直接的相互作用，并进一步优化了模型构建条件。化合物黑毛霉素（chetomin）、甲萘醌（menadione）在此筛选模型上能抑制其相互作用。在此基础上，联合u251-hre的hif-1转录活性抑制剂筛选方法，充分肯定了黑毛霉素能有效抑制hif-1活性。因此，联合哺乳动物双杂交和u251-hre这两个细胞模型，成功建立了以hif-1α和p300相互作用为靶点的筛选模型，为特异性小分子肿瘤靶向药物的开发奠定了基础。
| [1] | ackert,platekh.hypoxiaandhypoxiainduciblefactors(hif)asimportantregulatorsoftumorphysiology[j].cancertreatres,2004,117:219-248.
|
| [2] | chichej,riccije,pouyssegurj.tumorhypoxiaandmetabolism-towardsnovelanticancerapproaches[j].annendocrinol(paris),2013,74:111-114.
|
| [3] | semenzagl.hif-1andhumandisease:onehighlyinvolvedfactor[j].genesdev,2000,14:1983-1991.
|
| [4] | onnisb,rapisardaa,melillog.developmentofhif-1inhibitorsforcancertherapy[j].jcellmolmed,2009,13:2780-2786.
|
| [5] | wardc,langdonsp,mullenp,etal.newstrategiesfortargetingthehypoxictumourmicroenvironmentinbreastcancer[j].cancertreatrev,2013,39:171-179.
|
| [6] | wud,zhangr,zhaor,etal.anovelfunctionofnovobiocin:disruptingtheinteractionofhif1alphaandp300/cbpthroughdirectbindingtothehif1alphac-terminalactivationdomain[j].plosone,2013,8:e62014.
|
| [7] | nayr,hankc,parkh,etal.menadioneandethacrynicacidinhibitthehypoxia-induciblefactor(hif)pathwaybydisruptinghif-1alphainteractionwithp300[j].biochembiophysrescommun,2013,434:879-884.
|
| [8] | langlw,tangk,liy,etal.identificationoftwosmallmoleculeinhibitorsofhypoxia-induciblefactor1withdifferentcell-basedscreeningmodel[j].chinajchinmatermed(中国中药杂志),2012,37:2151-2155.
|
| [9] | xiay,choihk,leek.recentadvancesinhypoxia-induciblefactor(hif)-1inhibitors[j].eurjmedchem,2012,49:24-40.
|
| [10] | semenzagl.evaluationofhif-1inhibitorsasanticanceragents[j].drugdiscovtoday,2007,12:853-859.
|
| [11] | rapisardaa,uranchimegb,scudieroda,etal.identificationofsmallmoleculeinhibitorsofhypoxia-induciblefactor1transcriptionalactivationpathway[j].cancerres,2002,62:4316-4324.
|
| [12] | melillog.inhibitinghypoxia-induciblefactor1forcancertherapy[j].molcancerres,2006,4:601-605.
|
| [13] | kungal,zabludoffsd,franceds,etal.smallmoleculeblockadeoftranscriptionalcoactivationofthehypoxia-induciblefactorpathway[j].cancercell,2004,6:33-43.
|
| [14] | freedmansj,sunzy,poyf,etal.structuralbasisforrecruitmentofcbp/p300byhypoxia-induciblefactor-1alpha[j].procnatlacadsciusa,2002,99:5367-5372.
|
Full-Text
|
|
Contact Us
service@oalib.com QQ:3279437679 
WhatsApp +8615387084133
|
|
