申请人:LONDON DIAGNOSTICS, INC.
公开号:EP0322926A2
公开(公告)日:1989-07-05
In accordance with the present invention, specific binding assays are disclosed which utilize an chemiluminescent compound, i.e., moiety, which has increased stability in aqueous solution. The chemiluminescent moiety is an ester, thioester or amide in which the ester, thioester or amide linkage is between (1) a heterocyclic ring or ring system containing a carbon atom to which the linkage is attached, wherein the heteroatom within the heterocyclic ring or ring system is in an oxidation state which renders such carbon atom susceptible to attack by peroxide or molecular oxygen to form an intermediate which decays to produce chemiluminescence, and (2) an aryl ring or ring system. The aryl ring or ring system contains at least one substituted six-member ring. The substituted six-member ring has two or more substituent groups, where at least two of said two or more substituent groups sterically hinder hydrolysis of said linkage. One or more of the substituent groups which sterically hinder hydrolysis of said linkage may be an electron withdrawing group. The substituted six-member ring may have one or more additional substituent groups in addition to the substituent groups which sterically hinder hydrolysis of the linkage. Such additional substituent groups may also be an electron withdrawing group.
The carbon atoms in the heterocyclic ring or ring system, to which the linkage is attached, may also have a secondary substituent of the formula RnX-, where X is selected from the group consisting of O, N, S and C, where R is any group, and where n is a number such that X has proper valency. Other chemiluminescent moieties are disclosed which are characterized by a heterocyclic ring or ring system and a secondary substituent of the formula RnX-, with the ester, thioester or amide linkage being between the heterocyclic ring or ring system and a leaving group. The disclosed chemiluminescent moieties can also include substituents at peri positions within the heterocyclic ring or ring system.
Also in accordance with the present invention, compositions including and assay kits incorporating such chemiluminescent moieties are disclosed.
根据本发明,公开了利用化学发光化合物(即在水溶液中稳定性更强的分子)进行特异性结合测定的方法。化学发光分子是酯类、硫酯类或酰胺类,其中酯类、硫酯类或酰胺类连接在 (1) 杂环或环系之间,杂环或环系含有一个碳原子,连接在该碳原子上,杂环或环系中的杂原子处于氧化状态,使该碳原子易受过氧化物或分子氧的侵蚀而形成中间体,中间体衰变产生化学发光;(2) 芳环或环系。芳基环或环系统包含至少一个取代的六元环。取代的六元环具有两个或两个以上的取代基,其中至少有两个取代基在立体上阻碍了所述连接的水解。其中一个或多个取代基团可以是取电子基团,这些取代基团立体地阻碍了所述连接的水解。取代的六元环除了具有立体阻碍水解连接的取代基团外,还可以具有一个或多个额外的取代基团。这些额外的取代基团也可以是取电子基团。
连接该连接体的杂环或环系中的碳原子也可以具有式 RnX- 的仲取代基,其中 X 选自 O、N、S 和 C 组成的组,R 为任意基团,n 为使 X 具有适当价数的数字。还公开了其他化学发光分子,其特征在于杂环或环系和式 RnX- 的仲取代基,酯、硫酯或酰胺连接在杂环或环系和离去基团之间。所公开的化学发光分子还可以包括杂环或环系周围位置的取代基。
根据本发明,还公开了包含此类化学发光分子的组合物和检测试剂盒。