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    • 7. 发明授权
    • Phenylboronic acid complexing reagents derived from aminosalicylic acid
    • 衍生自氨基水杨酸的苯硼酸络合试剂
    • US5688928A
    • 1997-11-18
    • US480970
    • 1995-06-07
    • Mark L. Stolowitz
    • Mark L. Stolowitz
    • C07C229/38C07C233/49C07C233/51C07C237/12C07C237/22C07C255/13C07C259/10C07C271/22C07C281/02C07D207/44C07D207/452C07D207/46C07D213/71C07F5/02C07F5/04C07K5/02G01N33/543
    • C07D207/452C07C229/38C07C233/49C07C233/51C07C237/12C07C237/22C07C255/13C07C259/10C07C271/22C07C281/02C07D207/46C07D213/71C07F5/025C07K5/0207G01N33/54353
    • The present invention relates to a novel class of phenylboronic acid complexing reagents useful for the preparation of bioconjugates, and the method of making and using such reagents. In the present invention, in the place of prior art Avidin-Biotin and Digoxigenin-anti-Digoxigenin systems, phenylboronic acid complexing reagents are utilized in conjunction with phenylboronic acid reagents (many of which are known in the prior art) to facilitate chemical conjugation without the use of intermediary biological macromolecules. Reagents suitable for the modification of bioactive species for the purpose of incorporating a phenylboronic acid complexing moiety for subsequent conjugation to a different bioactive species having pendant phenylboronic acid moieties are of General Formula I or General Formula II. ##STR1## wherein group X is selected from either H, OH, NH.sub.2, NHCH.sub.3, NHOH and NHOCH.sub.3, wherein group Y is selected from either O, S, and NH, and wherein group Z comprises a spacer which either separates the boronic acid complexing moiety from group R, as in General Formula I, or seperates two boronic acid complexing moieties, as in General Formula II. Group R is a reactive electrophilic or nucleophilic moiety suitable for reaction of the phenylboronic acid complexing reagent with a bioactive species.
    • 本发明涉及可用于制备生物缀合物的新一类苯基硼酸络合剂,以及制备和使用这些试剂的方法。 在本发明中,代替现有技术的抗生物素蛋白 - 生物素和地高辛 - 抗地高辛系统,苯硼酸络合试剂与苯硼酸试剂(许多已知在现有技术中)一起使用,以促进化学共轭而没有 使用中间生物大分子。 适于修饰生物活性物质的试剂为通式I或通式II,其用于将苯硼酸络合部分并入用于随后缀合至具有侧苯基硼酸部分的不同生物活性物质的目的。 通式I其中基团X选自H,OH,NH 2,NHCH 3,NHOH和NHOCH 3,其中基团Y选自O,S和NH,并且其中基团Z包括 如通式I所示,将硼酸络合部分与基团R分开的间隔物,或分离两个硼酸络合部分,如通式II所示。 基团R是适用于苯基硼酸络合试剂与生物活性物质反应的反应性亲电或亲核部分。
    • 8. 发明授权
    • Phenylboronic acid complexes for bioconjugate preparation
    • 苯硼酸复合物用于生物缀合物的制备
    • US5677431A
    • 1997-10-14
    • US482886
    • 1995-06-07
    • Mark L. Stolowitz
    • Mark L. Stolowitz
    • C07F5/02G01N33/543
    • C07F5/025G01N33/54353
    • The present invention relates to a novel class of phenylboronic acid bioconjugate complexes derived from aminosalicylic acid, and the method of making and using such bioconjugate complexes. The bioconjugate complexes are in the form of the following general formulas; ##STR1## wherein group X is selected from the group consisting of O, NH, N-alkyl, NC.sub.6 H.sub.5, N-aryl, NCH.sub.2 -aryl, NCH.sub.2 CH.sub.2 OH, NCOCH.sub.2 CH.sub.2 OH, NOH, NO-alkyl and NOCH.sub.2 -aryl, wherein alkyl denotes a hydrocarbon moiety of from 1 to 4 carbons in length and which may be linear or branched, wherein aryl is selected from the group consisting of an aromatic ring, a substituted aromatic ring and a fused aromatic ring, wherein group Y is selected from the group consisting of O, S, NH, N-alkyl, N-aryl and NCH.sub.2 -aryl, wherein groups Z and Z* comprise a spacer selected from an alkyl and a polyethyleneglycol chain, of from 1 to 16 carbon equivalents in length, wherein the chain may contain intermediate amide and disulfide bonds, and and wherein groups BAS and BAS* are bioactive species.
    • 本发明涉及一类新型的衍生自氨基水杨酸的苯基硼酸生物缀合物复合物,以及制备和使用这种生物缀合物复合物的方法。 生物共轭配合物为下列通式的形式: 通用化学式I GE>通式III + TR 通式IV + TR 其中基团X选自O,NH,N-烷基,NC6H5,N-芳基 ,NCH 2 - 芳基,NCH 2 CH 2 OH,NCOCH 2 CH 2 OH,NOH,NO-烷基和NOCH 2 - 芳基,其中烷基表示长度为1至4个碳的烃部分,其可以是直链或支链的,其中芳基选自 芳香环,取代芳环和稠合芳环,其中基团Y选自O,S,NH,N-烷基,N-芳基和NCH 2 - 芳基,其中基团Z和Z *包含 选自烷基和聚乙二醇链的间隔长度为1至16碳当量的链,其中该链可含有中间体酰胺和二硫键,并且其中gro
    • 9. 发明授权
    • Phenylboronic acid complexing reagents derived from aminosalicylic acid
    • 衍生自氨基水杨酸的苯硼酸络合试剂
    • US5594151A
    • 1997-01-14
    • US188531
    • 1994-01-28
    • Mark L. Stolowitz
    • Mark L. Stolowitz
    • C07C229/38C07C233/49C07C233/51C07C237/12C07C237/22C07C255/13C07C259/10C07C271/22C07C281/02C07D207/44C07D207/452C07D207/46C07D213/71C07F5/02C07F5/04C07K5/02G01N33/543
    • C07D207/452C07C229/38C07C233/49C07C233/51C07C237/12C07C237/22C07C255/13C07C259/10C07C271/22C07C281/02C07D207/46C07D213/71C07F5/025C07K5/0207G01N33/54353
    • The present invention relates to a novel class of phenylboronic acid complexing reagents useful for the preparation of bioconjugates, and the method of making and using such reagents. In the present invention, in the place of prior art Avidin-Biotin and Digoxigenin-anti-Digoxigenin systems, phenylboronic acid complexing reagents are utilized in conjunction with phenylboronic acid reagents (many of which are known in the prior art) to facilitate chemical conjugation without the use of intermediary biological macromolecules. Reagents suitable for the modification of a bioactive species for the purpose of incorporating a phenylboronic acid complexing moiety for subsequent conjugation to a different bioactive species having pendant phenylboronic acid moleties are of General Formula I or General Formula II. ##STR1## wherein group X is selected from either H, OH, NH.sub.2, NHCH.sub.3, NHOH and NHOCH.sub.3, wherein group Y is selected from either O, S and NH, and wherein group Z comprises a spacer which either separates the boronic acid complexing moiety from group R, as in General Formula I, or seperates two boronic acid complexing moieties, as in General Formula II. Group R is a reactive electrophilic or nucleophilic moiety suitable for reaction of the phenylboronic acid complexing reagent with a bioactive species.
    • 本发明涉及可用于制备生物缀合物的新一类苯基硼酸络合剂,以及制备和使用这些试剂的方法。 在本发明中,代替现有技术的抗生物素蛋白 - 生物素和地高辛 - 抗地高辛系统,苯硼酸络合试剂与苯硼酸试剂(许多已知在现有技术中)一起使用,以促进化学共轭而没有 使用中间生物大分子。 适于修饰生物活性物质的试剂为通式I或通式II,其用于将苯硼酸络合部分并入用于随后与不同具有侧苯基硼酸汽车侧生物活性物质的缀合物。 通式I其中基团X选自H,OH,NH 2,NHCH 3,NHOH和NHOCH 3,其中基团Y选自O,S和NH,并且其中基团Z包含 如通式I那样将硼酸络合部分与基团R分开的间隔物,或分离两个硼酸络合部分,如通式II所示。 基团R是适用于苯基硼酸络合试剂与生物活性物质反应的反应性亲电或亲核部分。