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ID:23531795
大小:4.12 MB
页数:52页
时间:2018-11-08
《分子模拟技术筛选抗hiv-1逆转录酶活性化合物》由会员上传分享,免费在线阅读,更多相关内容在学术论文-天天文库。
1、screeningmethodhassomereliabiiityandaccuracy.9.Virtualresultsshowthecompoundspossessingthehigherscores.formedhydrogenbondswiththeresiduesLysl01andⅡ一ⅡstackinginteractiOIlSwiththeresiduesTYRl81,TRP229,andhorseshoeshapeddockingconformationmoleculeshavethegreaterpossibilityto
2、inhibitagainsttheHIV一1reversetranscriptase.10.InthiSpaper,the25compoundswastestedbytheanti—IIIV1bioassayinvitro.andtheresultsshowedthatthe25compoundshaveanti—HIV—lacLiviLy,ofwhichtheEC50ofthe10compoundswaslessthanlOug/ml,andtheTIofj一(4fluorophenyl)3[2(11{indol一3一y1)ethyl]
3、thioureaand6一[[5一(4一chloroanilino)一1,3,4一thiadiazol一2一y1]methoxy]一4一methylchromen一2一onewasgreaterthan10.11.Thevirtualandbioassaytestresultsshowedthatthedockingconformationofl一(4一fluorophenyl)一3一[2一(1H—indol一3一y1)ethyl]thioureaWaSwellalignedwiththe1jgandofthecrystalcomplex
4、of2ZDlandpresentedtheUshapedstructure.ItformedthehydrogenbondswiththekeyresidueLysl01andtheⅡ一Ⅱstackinginteractions、viththeconservativeresidueTrp229andthearomaticresidueTyrl81inthebindingpocketofHIV1reversetranscriptasewerealsoobserved.ThebioassayinvitroshowedTheCC50valueo
5、fthecompoundWaSgreaterthani00,itsEC50valuewas4.54ug/ml,anditstherapeuticindex(TI)isgreaterthan18.35.Thedockingconformationof6一[[5一(4一chloroanilino)一l,3.4thiadiazol一2一y1]methoxy]一4-methylchI’olnen一2一onewaspresentedthehorseshoeshapedstructureandwel1alignedwiththeligandinthe
6、crystalcomplex.ItformedthehydrogenbondswiththekeyresidueLysl01、Lysl03andtheⅡ一ⅡstackinginteractionswiththeconservatireresidueTrp229andthearomaticresidueTyrl81inthebindingpocketofHIV——1reversetranscriptasewerealSOobserved.ThebioassayinvitroshowedtheCC50value0fIthecompoundwa
7、sgreaterthan100,theEC50was9.85ug/ml,anditstherapeuticindex(TI)iSgreaterthanlO.i5.TheconclusionthatthevirtualrcsultsareingoodagreementwiththebioassayexperimentfullYprovidesthereljabi¨tyofthevirtualmethod.ConcIUSion:1.Fromthecompoundstructure,theflexihieUandhorseshoeshapeds
8、tructureofnon——nucleosidereversetranscriptaseinhibitorscanadapttothebingdingpocketchangeofthetlI
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