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1. 发明公开

EP2354153A2 Stable peptide mimetic of HIV gp41 fusion intermediate 审中-公开
标题翻译： Stabiles Peptidmimetikum des HIV-gp41-Fusionszwischenprodukts
公开(公告)号：EP2354153A2
公开(公告)日：2011-08-10
申请号：EP11154574.5
申请日：2005-05-27
申请人： Merck Sharp & Dohme Corp. , Istituto Di Ricerche Di Biologia Molecolare S.P.A.
发明人： Bianchi, Elisabetta , Pessi, Antonello , Geleziunas, Romas , Bramhill, David
IPC分类号： C07K14/16
CPC分类号： C07K14/005 , A61K38/00 , A61K39/00 , A61K39/12 , C12N2740/15022 , C12N2740/16122 , C12N2740/16134 , G01N2333/16 , G01N2500/02
摘要： Methods of covalently-stabilizing alpha-helical, chimeric peptides constrained within a homotrimeric or heterotrimeric coiled-coil structure are disclosed. The coiled-coil structures made by the methods disclosed within this specification mimic all or a portion of the internal, trimeric coiled-coil motif contained within the fusogenic conformation of an enveloped virus membrane-fusion protein, particularly the internal coiled-coil domain of the HIV gp41 ectodomain. The HIV-derived, chimeric peptides disclosed comprise a non-HIV, soluble, trimeric form of a coiled-coil fused in helical phase to all or a portion of the N-helix of HIV gp41 and are covalently-stabilized in a homotrimeric or heterotrimeric coiled-coil structure through the formation of disulfide or chemoselective bonds between said peptides. The covalently-stabilized, HIV-derived, homotrimeric or heterotrimeric coiled-coil structures made by the methods disclosed herein represent a close mimetic of a HIV gp41 fusion intermediate and are potent inhibitors of HIV infectivity. These HIV-derived chimeric peptides may provide for therapeutic treatment against HIV infection by inhibiting the virus-host cell membrane fusion process.
摘要翻译：公开了限制在同三聚体或异三聚体线圈结构内的共价稳定的α-螺旋嵌合肽的方法。通过本说明书中公开的方法制备的盘绕线圈结构模拟包含在包膜病毒膜融合蛋白的融合构象内的内部，三聚体卷曲线粒体的全部或一部分，特别是内部卷曲螺旋结构域 HIV gp41胞外域。所公开的HIV衍生的嵌合肽包含非HIV，可溶性三聚体形式的卷曲螺旋，其以螺旋相融合到HIV gp41的全部或部分N-螺旋，并且共价稳定在同三聚体或异三聚体通过在所述肽之间形成二硫键或化学选择性键来进行卷曲螺旋结构。通过本文公开的方法制备的共价稳定的HIV衍生，同源三聚体或异三聚体卷曲螺旋结构代表HIV gp41融合中间体的密切模拟物，并且是HIV感染性的有效抑制剂。这些HIV衍生的嵌合肽可以通过抑制病毒宿主细胞膜融合过程来提供针对HIV感染的治疗性治疗。

2. 发明公开

EP2354153A3 Stable peptide mimetic of HIV gp41 fusion intermediate 审中-公开
标题翻译：的HIV gp41融合中间体的稳定肽模拟物
公开(公告)号：EP2354153A3
公开(公告)日：2012-05-30
申请号：EP11154574.5
申请日：2005-05-27
申请人： Merck Sharp & Dohme Corp. , Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A.
发明人： Bianchi, Elisabetta , Pessi, Antonello , Geleziunas, Romas , Bramhill, David
IPC分类号： C07K14/16
CPC分类号： C07K14/005 , A61K38/00 , A61K39/00 , A61K39/12 , C12N2740/15022 , C12N2740/16122 , C12N2740/16134 , G01N2333/16 , G01N2500/02
摘要： Methods of covalently-stabilizing alpha-helical, chimeric peptides constrained within a homotrimeric or heterotrimeric coiled-coil structure are disclosed. The coiled-coil structures made by the methods disclosed within this specification mimic all or a portion of the internal, trimeric coiled-coil motif contained within the fusogenic conformation of an enveloped virus membrane-fusion protein, particularly the internal coiled-coil domain of the HIV gp41 ectodomain. The HIV-derived, chimeric peptides disclosed comprise a non-HIV, soluble, trimeric form of a coiled-coil fused in helical phase to all or a portion of the N-helix of HIV gp41 and are covalently-stabilized in a homotrimeric or heterotrimeric coiled-coil structure through the formation of disulfide or chemoselective bonds between said peptides. The covalently-stabilized, HIV-derived, homotrimeric or heterotrimeric coiled-coil structures made by the methods disclosed herein represent a close mimetic of a HIV gp41 fusion intermediate and are potent inhibitors of HIV infectivity. These HIV-derived chimeric peptides may provide for therapeutic treatment against HIV infection by inhibiting the virus-host cell membrane fusion process.

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