Biophysical Property and Broad Anti-HIV Activity of Albuvirtide, a 3-Maleimimidopropionic Acid-Modified Peptide Fusion Inhibitor 英文参考文献.docVIP

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Biophysical Property and Broad Anti-HIV Activity of Albuvirtide, a 3-Maleimimidopropionic Acid-Modified Peptide Fusion Inhibitor 英文参考文献.doc

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Biophysical Property and Broad Anti-HIV Activity of Albuvirtide, a 3-Maleimimidopropionic Acid-Modified Peptide Fusion Inhibitor 英文参考文献

BiophysicalPropertyandBroadAnti-HIVActivityof Albuvirtide,a3-MaleimimidopropionicAcid-Modified PeptideFusionInhibitor HuihuiChong1,XueYao1,ChaoZhang1,LifengCai2,ShengCui1,YouchunWang3,YuxianHe1* 1Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 2Beijing Institute of Pharmacology and Toxicology,Beijing,China,3NationalInstitutefortheControlofPharmaceuticalandBiologicalProducts,Beijing,China Abstract Albuvirtide (ABT) is a 3-maleimimidopropionic acid (MPA)-modified peptide HIV fusion inhibitor that can irreversibly conjugatetoserumalbumin.Previousstudiesdemonstrateditsinvivolonghalf-lifeandpotentanti-HIVactivity.Here,we focusedtocharacterizeitsbiophysicalpropertiesandevaluateitsantiviralspectrum.IncontrasttoT20(Enfuvirtide,Fuzeon), ABTwasabletoformastablea-helicalconformationwiththetargetsequenceandblockthefusion-activesix-helixbundle (6-HB)formationinadominant-negativemanner.ItefficientlyinhibitedHIV-1Env-mediatedcellmembranefusionandvirus entry. A large panel of 42 HIV-1 pseudoviruses with different genotypes were constructed and used for the antiviral evaluation.TheresultsshowedthatABThadpotentinhibitoryactivityagainstthesubtypesA,BandCthatpredominatethe worldwideAIDSepidemics,andsubtypeB9,CRF07_BCandCRF01_AErecombinantsthatarecurrentlycirculatinginChina. Furthermore,ABTwasalsohighlyeffectiveagainstHIV-1variantsresistanttoT20.Takentogether,ourdataindicatethatthe chemicallymodifiedpeptideABTcanserveasanidealHIV-1fusioninhibitor. Citation:ChongH,YaoX,ZhangC,CaiL,CuiS,etal.(2012)BiophysicalPropertyandBroadAnti-HIVActivityofAlbuvirtide,a3-MaleimimidopropionicAcid- ModifiedPeptideFusionInhibitor.PLoSONE7(3):e32599.doi:10.1371/journal.pone.0032599 Editor:PhilippeGallay,ScrippsResearchInstitute,UnitedStatesofAmerica ReceivedOctober21,2011;AcceptedJanuary27,2012;PublishedMarch5,2012 Copyright: ? 2012 Chong et al. This is an open-access article distributed under the terms of the Creative Commons Attributio