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    • 7. 发明申请
    • On-Resin Peptide Cyclization
    • 树脂上的肽循环
    • US20080200647A1
    • 2008-08-21
    • US11665537
    • 2005-10-18
    • Stephane VarrayOleg WerbitzkyThomas Zeiter
    • Stephane VarrayOleg WerbitzkyThomas Zeiter
    • C07K1/06C07K7/00
    • C07K1/06C07K1/04
    • Method of peptide synthesis, comprising the steps of a. synthesizing a peptide linked to a solid phase which peptide comprises at least one cysteine, homo- or nor-cysteine residue, which cysteine is protected in its side chain by a S-tert.butyl-sulphenyl group b. either coupling N-terminally a further amino acid having a 3,3′-dithio-(1-carboxy-propyl)-propionyl-radical on its Nα or deprotecting the Nα of the N-terminal amino acid and reacting the free Nα with 3,3′-dithio-propionic acid imide to yield the corresponding Nα-3,3′-dithio-(1-carboxy-propyl)-propionamide or deprotecting the Nα of the N-terminal amino acid and reacting the free Nα with a compound of formula IV R7-S—S—[CH2]2—COOH IV wherein R7 is aryl-, including heteronuclear aryl, or is aralkyl-, alkylaryl- or alkyl-, which may be further substituted with halogeno, amido, ester, carboxy or ether, and c. reacting the peptide with a S-tert.Butyl-sulphenyl-protection group removing reagent, and d. cyclizing the peptide by means of disulfide bond formation, preferably cyclizing the peptide in the presence of air and/or oxygen.
    • 肽合成方法,包括以下步骤:a。 合成与固相连接的肽,该肽包含至少一个半胱氨酸,同型或半胱氨酸残基,该半胱氨酸在其侧链中被S-叔丁基 - 苯硫基b保护。 在其Nalpha上N末端连接另外具有3,3'-二硫代 - (1-羧基 - 丙基) - 丙酰基的氨基酸,或者使N-末端氨基酸的Nalpha去保护,并将游离Nalpha与3 ,3'-二硫代丙酸酰亚胺,得到相应的Nalpha-3,3'-二硫代 - (1-羧基 - 丙基) - 丙酰胺或使N末端氨基酸的Nalpha去保护并使游离Nalpha与化合物 其中R 7是芳基 - ,包括杂芳基,或是芳烷基 - ,烷基芳基 - 或烷基 - , - 其可以进一步被卤代,酰胺基,酯,羧基或醚取代,和c。 使肽与S-叔丁基 - 苯基 - 保护基团去除试剂反应,d。 通过形成二硫键使肽环化,优选在空气和/或氧存在下使肽环化。