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    • 8. 发明授权
    • Stable analogs of bioactive peptides containing disulfide linkages
    • 含有二硫键的生物活性肽的稳定类似物
    • US06664367B1
    • 2003-12-16
    • US08278437
    • 1994-07-21
    • Raghavan RajagopalanAnanthachari SrinivasanLeon R. Lyle
    • Raghavan RajagopalanAnanthachari SrinivasanLeon R. Lyle
    • C07K1600
    • C07K14/655C07K1/006C07K7/16C07K14/52C07K14/6555C07K14/70Y10S930/28
    • Stable analogs of cyclic peptides containing disulfide linkages are disclosed. The disulfide linkage is modified by one of four methods: (a) sulfide contraction, (b) isosteric substitution, (c) thioketal expansion, or (d) alkylation expansion. In sulfide contraction the disulfide bond (—S—S—) is replaced with a monosulfide bond (—S—) in which a bifunctional effector molecule, such as a ligand or chemotoxic agent, is bound to the new peptide linkage. In isosteric substitution, one sulfur atom is replaced with a carbon atom and at least one of the carbon atoms at the modified site is a bifunctional effector molecule. In thioketal expansion, an alkylidene unit (—CR1C2—) is inserted between the two sulfur atoms. In alkylation expansion, an alkyl moiety of from C2 to C3, is inserted between the two sulfur atoms.
    • 公开了含有二硫键的环肽的稳定类似物。 二硫键通过四种方法之一进行改性:(a)硫化物收缩,(b)等排取代,(c)硫代缩酮扩展或(d)烷基化扩展。 在硫化物收缩中,二硫键(-S-S-)用单硫键(-S-)代替,其中双功能效应分子如配体或化学毒性剂与新的肽键结合。 在等排取代中,一个硫原子被碳原子取代,并且在修饰位点处的至少一个碳原子是双功能效应子分子。 在硫缩酮扩展中,在两个硫原子之间插入亚烷基单元(-CR1C2-)。 在烷基化扩展中,C2至C3的烷基部分插入在两个硫原子之间。