发明授权
- 专利标题: Means and methods of enhancing delivery to biological systems
- 专利标题(中): 增强对生物系统传播的手段和方法
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申请号: US12443236申请日: 2007-09-26
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公开(公告)号: US09211340B2公开(公告)日: 2015-12-15
- 发明人: Paolo Botti
- 申请人: Paolo Botti
- 代理机构: Pillsbury Winthrop Shaw Pittman LLP
- 优先权: EP06020286 20060927; EP07013218 20070705
- 国际申请: PCT/EP2007/008396 WO 20070926
- 国际公布: WO2008/037463 WO 20080403
- 主分类号: A61K47/48
- IPC分类号: A61K47/48
摘要:
This invention relates to a peptide or polypeptide (a) which is esterified or thio-esterified (i) at the carboxylate of the C-terminus with a guanidinium alkanol, a guanidinium alkanethiol, a PEG substituted with a guanidinium group and having a free hydroxyl group, or a PEG substituted with a guanidinium group and a sulfhydryl group; (ii) at a side-chain carboxylate of one or more Asp or GIu residues, if present, with a guanidinium alkanol, a guanidinium alkanethiol, a PEG substituted with a guanidinium group and having a free hydroxyl group, or a PEG substituted with a guanidinium group and a sulfhydryl group; (iii) at a hydroxyl group of one or more Ser, Thr or Tyr residues, if present, with a guanidinium alkanoic acid or a PEG substituted with a guanidinium group and a carboxyl group; (iv) at a sulfhydryl group of one or more Cys residues, if present, with a guanidinium alkanoic acid or a PEG substituted with a guanidinium group and a carboxyl group; and/or (v) at the N-terminus with a guanidinium alkanoic acid or a PEG substituted with a guanidinium group and a carboxyl group, wherein said N-terminus is previously amidated with an alpha- or beta-hydroxy acid, and wherein the ester is formed between the hydroxy group of said alpha- or beta-hydroxy acid and the carboxylic group of said guanidinium alkanoic acid or said PEG substituted with a guanidinium group and a carboxyl group; and/or (b) which contains one or more disulfides, the disulfide being formed between the sulfhydryl group of a Cys reside, if present, and a guanidinium alkanethiol or a PEG substituted with a guanidinium group and a sulfhydryl group.
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