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	Quaternary protein mimetics of gp41 elicit neutralizing antibodies against HIV fusion-active intermediate state
	Sadler, Kristen ; Zhang, Ying ; Xu, Jiaxi ; Tam, James P.
	2008
DOI	10.1002/bip.20979
英文摘要	During viral entry, the fusogenic state of human immunodeficiency virus Type 1 (HIV-1) envelope protein gp4l is a quaternary structure consisting of three gp41 glycoproteins, each with two conserved helical domains (N-HR and C-HR). Thus far, the examination of monomeric gp41 peptides as an immunologically focused approach to vaccine design has not been successful. Here we report an approach using quaternary protein mimetics (called 3?? mimetics) that are based on the gp41 N-HR and C-HR domains to closely mimic the fusogenic state and overcome the deficiencies of the monomeric peptide approach for synthetic vaccine design. The 3?? mimetics are conveniently prepared by chemoselective ligation of unprotected monomeric peptides to an interstrand linker, and display enhanced conformational stability compared to the corresponding monomers. The 3?? mimetics with or without a covalently attached T-helper epitope were immunogenic and elicited antisera that bound both recombinant gp160, which contains gp41, and HIV-1 virions and immunoprecipitated recombinant gp41. Anti-3?? mimetic antisera neutralized viral infectivity against R5- and X4-tropic strains of HIV-1 at 31.5??C. The results suggest that a quaternary protein approach to mimic conserved andfunctional domains of viral envelope proteins is desirable for HIV vaccine development as such antigens are more likely to produce immunologically-focused and broadly neutralizing antibody responses. ?2008 Wiley Periodicals, Inc.; EI; 0; 3; 320-329; 90
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/408921]
专题	化学与分子工程学院
推荐引用方式 GB/T 7714	Sadler, Kristen,Zhang, Ying,Xu, Jiaxi,et al. Quaternary protein mimetics of gp41 elicit neutralizing antibodies against HIV fusion-active intermediate state[J],2008.
APA	Sadler, Kristen,Zhang, Ying,Xu, Jiaxi,&Tam, James P..(2008).Quaternary protein mimetics of gp41 elicit neutralizing antibodies against HIV fusion-active intermediate state..
MLA	Sadler, Kristen,et al."Quaternary protein mimetics of gp41 elicit neutralizing antibodies against HIV fusion-active intermediate state".(2008).

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