CN111537451B - 6-磷酸葡萄糖脱氢酶突变体及其在制备他克莫司检测试剂中的用途 - Google Patents
6-磷酸葡萄糖脱氢酶突变体及其在制备他克莫司检测试剂中的用途 Download PDFInfo
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Abstract
本申请涉及6‑磷酸葡萄糖脱氢酶突变体及其在制备他克莫司检测试剂中的用途。具体而言,本申请的6‑磷酸葡萄糖脱氢酶突变体相较于野生型6‑磷酸葡萄糖脱氢酶包含选自以下的一个突变或其组合:D306C、D375C、G426C。使用本申请的6‑磷酸葡萄糖脱氢酶突变体所制备的检测试剂盒,其特异性强、灵敏度高、操作方便、检测时间短、定量准确,适合高通量检测。
Description
本申请要求2019年1月9日提交的申请号为201910017764.4和2019年5月21日提交的申请号为201910423122.4《6-磷酸葡萄糖脱氢酶突变体及其在制备检测试剂中的用途》的优先权,其通过引用并入此处。
技术领域
本申请涉及生物检测领域,特别是涉及一种突变的酶6-磷酸葡萄糖脱氢酶(简称G6PDH)及其在他克莫司检测试剂盒中的应用。
背景技术
半抗原,某些小分子物质(分子量小于4000Da),其单独不能诱导免疫应答,即不具备免疫原性,但当其与大分子蛋白质或非抗原性的多聚赖氨酸等载体交联或结合后可获得免疫原性,诱导免疫应答。这些小分子物质可与应答效应产物结合,具备抗原性,它只有免疫反应性,不具免疫原性,又称不完全抗原。
半抗原能与对应抗体结合出现抗原-抗体反应,又不能单独激发人或动物体产生抗体的抗原。它只有免疫反应性,不具免疫原性,又称不完全抗原。大多数多糖、类脂、激素、小分子药物都属于半抗原。如果用化学方法把半抗原与某种蛋白分子(载体)结合,会获得新的免疫原性,并能刺激动物产生相应的抗体。
小分子抗原或半抗原因缺乏可作夹心法的两个以上的位点,因此不能用双抗体夹心法进行测定,多采用竞争模式。原理是标本中的抗原和一定量的酶标抗原竞争与固相抗体结合。标本中抗原量含量愈多,结合在固相上的酶标抗原愈少,显色愈浅。小分子激素、药物等ELISA测定多用此法。
他克莫司(tacrolimus)作为半抗原的具体实例,结构式如下所示:
他克莫司又称FK506,是一种大环内酯类抗生素。1984年他克莫司在日本被发现,1989年作为免疫抑制剂首次应用于临床。他克莫司作为一种免疫抑制剂,具有很高的亲脂性,吸收不完全且不稳定。
他克莫司安全而有效的治疗范围很窄,他克莫司的剂量不足或者血药浓度过低可能会导致移植排斥反应。他克莫司浓度过高又会导致严重的不良反应,不良反应包括肾毒性、神经毒性、移植后糖尿病、对传染易感性增加、癌变、高血压、以及胃肠道功能紊乱等。
基于上述原因,他克莫司血药浓度监测,是辅助临床治疗、改善治疗效果、降低毒性风险的有效方式。
目前已知的他克莫司检测方法主要有:高效液相色谱法(HPLC)、发光免疫、酶联免疫吸附剂测定(ELISA)等方法。HPLC法需要复杂的样品前处理,操作复杂周期长且成本昂贵;发光免疫法试剂成本昂贵,不适合常规治疗药物检测,更不利于大范围推广。
现有的均相酶免疫测定法、胶乳凝集比浊法常常因制备工艺复杂、批间差大,应用受到一定限制。
现有技术CN108107200A描述了一种他克莫司检测试剂盒,其中公开了6-磷酸葡萄糖脱氢酶和他克莫司偶联物的制备方法:
-将20-100mg他克莫司溶于甲醇中,加入无水乙酸钠,溶解均匀后加入羧甲基羟胺,溶解混匀,氮气保护下加温反应过夜,然后减压蒸馏得蜡状物,加入二甲基甲酰胺溶解,过滤去除沉淀,减压蒸馏去除溶剂得产物A;
-用20-100mL二甲基甲酰胺溶解10-50mg产物A,再将50-150μL的碳二亚胺(EDC)在搅拌下缓慢滴加到上述溶液中,旋转混合60-150分钟;
-取10-50mg规格为100-300KU的6-磷酸葡萄糖脱氢酶的溶解于PBS缓冲液中震荡均匀;
-将他克莫司溶液在搅拌下缓慢加入到3溶液中,搅拌反应8-16小时,得到6-磷酸葡萄糖脱氢酶和他克莫司偶联物。
然而,现有技术的方法依赖于对小分子药物(他克莫司)自身所带反应基团进行的激活,之后再与酶进行反应。这样的偶联方法会出现同一葡萄糖六磷酸脱氢酶上链接有多个他克莫司的情况,且偶联位点难以确保一致性,难以保证小分子药物和酶之间的定向1:1反应,而导致批间差异大。
发明内容
鉴于本领域的需求,本申请提供了一种新型的6-磷酸葡萄糖脱氢酶突变体、及其在制备他克莫司检测试剂盒中的用途。
根据一些实施方案,提供了一种6-磷酸葡萄糖脱氢酶突变体。区别于已有发表的专利US006090567A(Homogeneous immunoassays using mutant glucose-6-phosphatedehydrogenases)的6磷酸葡萄糖脱氢酶的突变体,本申请的6-磷酸葡萄糖脱氢酶突变体,其包含选自以下的突变:D306C、G426C、D375C。
根据一些实施方案,提供了一种6-磷酸葡萄糖脱氢酶突变体,所述6-磷酸葡萄糖脱氢酶突变体是选自以下的序列所示:SEQ ID No.2、SEQ ID No.3、SEQ ID No.4。
根据一些实施方案,提供了一种多核苷酸,其编码本申请的6-磷酸葡萄糖脱氢酶突变体。
根据一些实施方案,提供了一种表达载体,其包含本申请的多核苷酸。
根据一些实施方案,提供了一种宿主细胞,其包含本申请的表达载体。宿主细胞可以是原核(如细菌)或真核(如酵母)。
根据一些实施方案,提供了一种偶联物,其是本申请的6-磷酸葡萄糖脱氢酶突变体与半抗原按照摩尔比1:x偶联而成。
在一些实施方案中,x是1至50,例如,1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、35、36、37、38、39、40、41、42、43、44、45、46、47、48、49、50。
在一些具体的实施方案中,本申请的6-磷酸葡萄糖脱氢酶突变体与半抗原按照摩尔比优选为1:1。
在一些具体的实施方案中,半抗原的分子量为100Da至4000Da,例如:100、150、200、250、300、350、400、410、420、430、440、450、460、470、480、490、500、520、550、570、600、620、650、700、750、800、850、900、950、1000、1100、1200、1300、1400、1500、1600、1700、1800、1900、2000、2100、2200、2300、2400、2500、2600、2700、2800、2900、3000、3100、3200、3300、3400、3500、3600、3700、3800、3900、4000。
根据本申请,技术人员将理解,“半抗原”还包含其衍生物的形式。为了便于和6-磷酸葡萄糖脱氢酶进行偶联,对于那些自身不带有偶联基团(例如,与巯基反应的基团)的半抗原(例如他克莫司),可以经改造而带有接头,以便和巯基共价结合。因此,在本申请中,半抗原衍生物是指,经改造而带有巯基反应基团的半抗原。
半抗原选自:小分子药物(如抗生素、精神药物)、激素、代谢物、糖、脂质、氨基酸。
半抗原例如但不限于:万古霉素、茶碱、苯妥英、维生素D、25羟维生素D、1,25双羟维生素D、叶酸、强心甙(包括地高辛、洋地黄毒苷)、酶酚酸、雷帕明、环胞菌素A、乙胺碘复酮、甲胺喋呤、他克莫司、血清氨基酸、胆汁酸、甘胆酸、苯丙氨酸、乙醇、尿尼柯丁代谢产物柯替宁、尿***、尿单羟酚衍生物、神经肽酪氨酸、血浆甘丙素、多胺、组织胺、促甲状腺激素、泌乳素、胎盘泌乳素、生长激素、促***、促***、促肾上腺皮质激素、抗利尿激素、降钙素、降钙素原、甲状旁腺激素、甲状腺素、三碘甲状原氨酸、反三碘甲状原氨酸、游离甲状腺素、游离三碘甲状原氨酸、皮质醇、尿17-羟皮质类固醇、尿17-酮类固醇、脱氢表雄酮及硫酸酯、醛固酮、尿香草苦杏仁酸、血浆肾素、血管紧张素、***、睾酮、双氢睾酮、雄烯二酮、17α羟孕酮、雌酮、雌三醇、***、孕酮、人绒毛膜***、胰岛素、胰岛素原、C肽、胃泌素、血浆***素、血浆6-酮***素F1α、前列环素、肾上腺素、儿茶酚胺、去甲肾上腺素、胆囊收缩素、纳素、环磷酸腺苷、环磷酸鸟苷、血管活性肽、生长抑素、促胰液素、P-物质、神经降压素、血栓素A2、血栓素B2、5羟色胺、神经肽Y、骨钙素。
在具体的实施方案中,半抗原是他克莫司或其衍生物。
在具体的实施方案中,半抗原是他克莫司衍生物,其带有巯基反应基团,例如来酰亚胺、溴乙酰基、乙烯基砜或氮丙啶。
在具体的实施方案中,半抗原是他克莫司衍生物,如式I所示:
在一些实施方案中,m为1至10的整数,优选1至6的整数,例如1、2、3、4、5、6。
根据一些实施方案,提供了一种试剂,其包含本申请的偶联物。
根据一些实施方案,提供了本申请的6-磷酸葡萄糖脱氢酶突变体在制备他克莫司检测试剂中的用途。
根据一些实施方案,提供了本申请的偶联物在制备他克莫司检测试剂中的用途。
在具体的实施方案中,所述的检测试剂选自:酶联免疫法检测试剂、化学发光免疫法检测试剂、均相酶免疫法检测试剂、胶乳增强免疫比浊法检测试剂。
在具体的实施方案中,所述的检测试剂优选是基于竞争法检测的试剂。
根据一些实施方案,提供了本申请的偶联物在制备他克莫司检测装置中的用途。
在具体的实施方案中,所述的检测装置可以制备成孔板(例如96-孔板)的形式,比如板上包被根据本申请的试剂。
在具体的实施方案中,所述的检测装置可以制备成颗粒(例如胶乳、磁珠)的形式,比如颗粒上包被根据本申请的试剂。
根据一些实施方案,提供了一种他克莫司检测试剂盒,其包含:
-第一试剂,所述第一试剂包含底物、缓冲液和他克莫司抗体;所述底物是6-磷酸葡萄糖脱氢酶的底物;
-第二试剂,所述第二试剂包含本申请的偶联物和缓冲液;
-任选地,校准品,所述校准品包含10mM至500mM缓冲液、0ng/ml至30ng/ml他克莫司;以及
-任选地,质控品,所述质控品包含10mM至500mM缓冲液、5ng/ml至25ng/ml他克莫司。
根据一个实施方案,提供了一种他克莫司检测试剂盒,其包含:
第一试剂,其包含:
10mM至500mM缓冲液、
5mM至50mM底物、
0.1μg/ml至10μg/ml mg/L他克莫司抗体、
0.1g/L至5g/L稳定剂、
0.1g/L至5g/L表面活性剂、
0.1g/L至5g/L防腐剂;
第二试剂,其包含:
10mM至500mM缓冲液、
0.1μg/ml至10μg/ml根据本申请的偶联物、
0.1g/L至5g/L稳定剂、
0.1g/L至5g/L表面活性剂、
0.1g/L至5g/L防腐剂;
第三试剂:其包含:甲醇与乙醇体积比为3:1的混合液、和0.5-5%的硫酸锌。
在一些实施方案中,所述缓冲液选自以下的一种或组合:TAPS、氨基丁三醇缓冲液、磷酸盐缓冲液、Tris-HCl缓冲液、柠檬酸-柠檬酸钠缓冲液、巴比妥缓冲液、甘氨酸缓冲液、硼酸盐缓冲液、三羟甲基甲烷缓冲液;优选地,磷酸盐缓冲液;所述缓冲液的浓度为10mmol/L至500mmol/L,优选50至100mM;所述缓冲液的pH为7至8。
在一些实施方案中,所述稳定剂选自以下的一种或组合:牛血清白蛋白、海藻糖、甘油、蔗糖、甘露醇、甘氨酸、精氨酸、聚乙二醇6000、聚乙二醇8000;优选牛血清白蛋白。
在一些实施方案中,所述表面活性剂选自以下的一种或组合:Brij23、Brij35、Triton X-100、Triton X-405、Tween20、Tween30、Tween80、椰子油脂肪酸二乙醇酰胺、AEO7,优选Tween20。
在一些实施方案中,所述的防腐剂选自以下的一种或组合:叠氮化物、MIT、生物防腐剂PC(如PC-300)、硫柳汞;所述叠氮化物选自:叠氮钠、叠氮锂。
在一些实施方案中,所述底物包含:6-磷酸葡糖糖、β-烟酰胺腺嘌呤二核苷酸。
在一些具体的实施方案中,所述他克莫司抗体源自:小鼠、大鼠、猫、犬、灵长类、牛、马、羊、骆驼科、禽、人。
在一些具体的实施方案中,所述他克莫司抗体选自:单抗、多抗、重组抗体、嵌合抗体、抗原结合片段。
根据一些实施方案,提供了一种偶联物的制备方法,包括步骤:
1)提供根据本申请的他克莫司衍生物,尤其是在非质子性溶剂(例如但不限于乙腈、二甲基甲酰胺、二甲基亚砜)中提供根据本申请的他克莫司衍生物;
2)提供6-磷酸葡萄糖脱氢酶突变体,优选在缓冲液(其提供反应环境,例如但不限于PBS、Tris、TAPS、TAPSO,所述缓冲液pH为6.0至8.0)中提供6-磷酸葡萄糖脱氢酶突变体;
3)在18℃至28℃,将所述他克莫司衍生物和所述6-磷酸葡萄糖脱氢酶突变体按照摩尔比n:1接触1小时至4小时(优选2小时至3小时)使得所述他克莫司衍生物和所述6-磷酸葡萄糖脱氢酶突变体发生偶联,得到所述种偶联物;
4)根据需要,任选对所述种偶联物进行纯化,例如脱盐处理等。
在一些实施方案中,反应体系中酶和半抗原的接触摩尔比1:n,其中n是1至500,例如,1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、35、36、37、38、39、40、41、42、43、44、45、46、47、48、49、50、100、200、300、400、500及其任意上述数值之间的范围;优选n是20至50。
在一些具体的实施方案中,步骤1)和2)可互换或并行。
在一些具体的实施方案中,在偶联之前,所述6-磷酸葡萄糖脱氢酶包含一个或多个游离的巯基,从而允许和他克莫司实现定向反应。
野生型6-磷酸葡萄糖脱氢酶不含游离的巯基,因此在一些具体的实施方案中,6-磷酸葡萄糖脱氢酶是经过基因工程改造的,使其在特定位点(306、375或426位)上的氨基酸突变为半胱氨酸,从而带有一个游离巯基。
附图说明
图1.G6PDH(野生型)氨基酸序列(SEQ ID No.1);源自假肠膜明串珠菌Leuconostoc pseudomesenteroides。
图2.G6PDH(D306C)氨基酸序列(SEQ ID No.2)。
图3.G6PDH(D375C)氨基酸序列(SEQ ID No.3)。
图4.G6PDH(G426C)氨基酸序列(SEQ ID No.4)。
具体实施方式
实施例
实施例1.他克莫司衍生物的合成
其中m=1。
向圆底烧瓶中加入他克莫司(100mg,0.11mmol),溶于干燥的DCM(5mL)中,向其中加入催化当量的4-N,N-二甲基吡啶,加入DCC(27mg,0.13mmol),氮气保护下,搅拌至全部溶解。向反应体系中加入4-马来酰亚胺丁酸(20mg,0.11mmol),室温(18℃至28℃,优选20℃至25℃)搅拌约4h,TLC检测。反应完毕直接用制备板纯化(MeOH/DCM=1:20),最终得到他克莫司衍生物(51mg,产率47%)。
按常规方法确认产物结构。
本实施例使得他克莫司带有一个可以和酶结合的基团。
实施例2.他克莫司衍生物与G6PDH分子的偶联
一、本申请的偶联方法
根据本申请的G6PDH-他克莫司偶联物,按照以下方式进行偶联:他克莫司衍生物分子上的巯基反应性基团(如但不限于马来酰亚胺基团)与G6PDH分子上的巯基共价结合。
1.将实施例1制备的他克莫司衍生物溶于N,N-二甲基甲酰胺中(10mg/ml);
2.G6PDH溶液:G6PDH(本申请的突变体或现有技术突变体)溶于PB 100mmol、NaCl100mmol、pH=8.0,5mg/mL酶;
3.将2ml葡萄糖6磷酸脱氢酶突变体溶液、7.5ml PB溶液和0.5ml他克莫司衍生物溶液;
4.上述混合溶液,在室温(18-28℃,优选20至25℃)下充分震荡2-3小时,脱盐处理(脱盐溶液100mM PB、0.1%NaN3、1%NaCl,pH=8.0),收集蛋白峰,所得产物即G6PDH-他克莫司偶联物。
二、对照偶联方法
参照CN108107200A实施例中公开的方法制备G6PDH-他克莫司偶联物:
1.将20-100mg他克莫司溶于甲醇中,加入无水乙酸钠,溶解均匀后加入羧甲基羟胺,溶解混匀,氮气保护下加温反应过夜,然后减压蒸馏得蜡状物,加入二甲基甲酰胺溶解,过滤去除沉淀,减压蒸馏去除溶剂得产物A;
2.用20-100mL二甲基甲酰胺溶解10-50mg产物A,再将50-150μL的碳二亚胺(EDC)在搅拌下缓慢滴加到上述溶液中,旋转混合60-150分钟;
3.取10-50mg规格为100-300KU的葡萄糖脱氢酶的溶解于PBS缓冲液中震荡均匀;
4.将上述步骤2的他克莫司溶液在搅拌下缓慢加入到步骤3溶液中,搅拌反应8-16小时。
实施例3.试剂盒的制备
制备以下检测他克莫司的试剂盒,其包含:
试剂R1,包含:
HEPES缓冲液50mM,PH 7.0
10mM 6-磷酸葡萄糖
10mMβ-烟酰胺腺嘌呤二核苷酸
1μg/ml他克莫司抗体(市售抗体)
1g/L牛血清白蛋白
1g/L Tween20
1g/L叠氮钠;
试剂R2,包括:
200mM Tris缓冲液,pH 8.0
1μg/ml G6PDH-他克莫司偶联物
1g/L牛血清白蛋白
1g/L Tween 20
1g/L叠氮钠;
样本萃取液:甲醇与乙醇体积比为3:1混合,和1%的硫酸锌;
校准品:20mM HEPES缓冲液,以及0.0、2.5、5.0、10.0、20.0、30.0ng/ml他克莫司(或按需加入);
质控品:20mM HEPES缓冲液,以及8.1ng/ml、15.4ng/ml、23.2ng/ml(或按需加入)。
将上述试剂(任选包含质控品、校准品),组装成他克莫司均相酶免疫检测试剂盒。
检测例
均相酶免疫测定的原理:在液体均相反应体系中,酶标记抗原(如G6PDH-他克莫司)与非标记抗原(他克莫司),竞争与定量的抗体(他克莫司抗体)进行结合,当抗体与非标记抗原结合越多,酶标记抗原释放的活性就越多,酶催化底物NAD+生成NADH就越多,在340nm波长下检测NADH的吸光度变化,即可推算出液体中他克莫司的含量。
将人全血样本和质控品、校准品完全混匀,用移液器取200μl样品到相应的离心管中,加入等体积的样本萃取液后立即盖上盖子,在漩涡震荡仪上震荡至少10秒,保证样本充分混匀,在离心机上以12000r/min的速度离心5分钟,将每份上清转到小管中并盖紧盖子,样本可用于检测。
表1.全自动生化仪参数
机型 | 日立7180参数 |
分析点 | [Rate-A][10][25][34] |
WAVE(SUB/MAIN) | [410][340] |
S.VIL. | [20] |
S.R1 | [150] |
S.R3 | [50] |
ABS.LIMIT: | [32000][递增] |
CALIB TYPE: | [Spline] |
POINT: | [6]SPAN PONIT[6] |
校准品 | 0.0、2.5、5.0、10.0、20.0、30.0ng/ml |
样本 | 待检样本,如血浆、血清、全血、尿液等 |
检测例1.本申请试剂盒的性能
1.定标吸光度
表2.定标吸光度
2.精密度实验
利用如上建立起的定标曲线,测定高、中、低质控品、临床样本。
表3.总不精密度
3.重复性
表4.盒重复性
4.回收
表5.回收
5.他克莫司检测试剂盒线性
表6.线性
6.他克莫司37℃试剂加速稳定性
本申请试剂37℃加速7天后,定标吸光度下降约16%,对照试剂37℃加速7天后,定标吸光度下降约51%。
表7.37℃试剂加速稳定性
检测例2.抗体抑制率
1.抗体抑制率的检测原理
当抗体与G6PDH-他克莫司偶联物结合时,由于空间位阻导致G6PDH酶活性受到影响,从而使得其催化NAD转化为NADH的效率降低,通过检测NADH量的变化,从而比较加入抗体与未加入抗体的实验组的差异,这种差异即体现为抗体对G6PDH的抑制能力。
2.反应体系
表8.抗体抑制率的检测试剂制备
3.结果
比较加入抗体与未加入抗体时,分别检测G6PDH-他克莫司偶联物吸光度测值,即可得到抗体对G6PDH的抑制情况。
相对于已发表的突变位点(A45C),本申请的突变体在抗体抑制率上有明显提高,能达到45%以上(G426C:45%;D375C:57%),最高达58%(D306C)。而之前已发表的突变位点(例如A45C、K55C)的抑制率为41%和25%。
表9.不同G6PDH突变体的抗体抑制率
虽然不限于具体理论,但是可以部分地解释为:和现有技术中的G6PDH突变体(A45C、K55C)相比,本申请酶突变体中突变位点(即引入游离巯基的位点)是和半抗原(比如激素、小分子药物等)发生偶联的位置所在。半抗原在这个位置上与半抗原特异性抗体结合时,所构成的空间位阻对G6PDH酶的活性影响最大,同时在引入突变后,还不能实质上影响分子的空间折叠。因此,这个突变位点的位置非常重要,需要同时兼顾G6PDH酶的活性、偶联分子的空间折叠、以及半抗原表位的充分暴露。
由于酶的突变体在抗体抑制率上有明显的提高。将酶的突变体与他克莫司偶联后的偶联物配制成试剂盒后,试剂在批间变异系数、线性、特异性等性能方面有明显的性能提升。
序列表
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Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110174363A (zh) * | 2019-01-09 | 2019-08-27 | 北京九强生物技术股份有限公司 | 6-磷酸葡萄糖脱氢酶突变体及其在制备检测试剂中的用途 |
CN113046335B (zh) * | 2019-12-27 | 2023-05-26 | 中国科学院天津工业生物技术研究所 | 一种仿生辅酶偏好性的葡萄糖6-磷酸脱氢酶突变体及其应用 |
WO2021139375A1 (zh) * | 2020-01-07 | 2021-07-15 | 北京九强生物技术股份有限公司 | 6-磷酸葡萄糖脱氢酶突变体及其在制备检测试剂中的用途 |
CN112114127A (zh) * | 2020-09-09 | 2020-12-22 | 武汉生之源生物科技股份有限公司 | 一种甘胆酸均相酶免疫测定试剂盒及其制备方法和应用 |
CN112225795A (zh) * | 2020-10-14 | 2021-01-15 | 湖南苏阳医疗科技有限公司 | 6-羟基硫酸褪黑素衍生物及其免疫原、特异性抗体的制备方法和应用 |
CN112574969A (zh) * | 2020-12-28 | 2021-03-30 | 郑州伊美诺生物技术有限公司 | G6pdh突变体及其应用 |
CN113567662A (zh) * | 2021-07-08 | 2021-10-29 | 重庆中元汇吉生物技术有限公司 | 一种测定甘胆酸的试剂盒及其制备方法 |
CN113736744B (zh) * | 2021-10-14 | 2023-07-18 | 江南大学 | 洋地黄毒苷单克隆抗体杂交瘤细胞株及其应用 |
CN115236216B (zh) * | 2022-06-07 | 2024-03-01 | 合肥和合医疗科技有限公司 | 高效液相色谱串联质谱检测全血中免疫抑制剂的试剂盒,其制备方法和检测方法 |
Family Cites Families (62)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2116301B1 (zh) * | 1970-12-07 | 1974-08-30 | Brun Lab Sa Le | |
US4190496A (en) * | 1971-05-14 | 1980-02-26 | Syva Company | Homogeneous enzyme assay for antibodies |
US3997525A (en) * | 1974-01-16 | 1976-12-14 | Bio-Tec, Inc. | Tetra-125 iodo-di-tyramine of digitalis derivative and process for making the same |
DE2901218A1 (de) * | 1979-01-13 | 1980-07-17 | Byk Gulden Lomberg Chem Fab | Ung von theophyllin |
JPS5618983A (en) * | 1979-07-25 | 1981-02-23 | Eisai Co Ltd | Theophylline derivative and its preapration |
US4262089A (en) * | 1980-04-07 | 1981-04-14 | Syva Company | Theophylline antigens and antibodies |
US4341866A (en) * | 1980-06-02 | 1982-07-27 | Syva Company | Antienzyme termination in enzyme immunoassays |
JPS57178159A (en) * | 1981-04-27 | 1982-11-02 | Banyu Pharmaceut Co Ltd | Chemical reagent for detection of amicacin and its determination |
US4608336A (en) * | 1981-08-27 | 1986-08-26 | Miles Laboratories, Inc. | #3B theophylline immunoassay employing 9-theophylline reagents |
US4469797A (en) * | 1982-09-23 | 1984-09-04 | Miles Laboratories, Inc. | Digoxigenin immunogens, antibodies, labeled conjugates, and related derivatives |
EP0119767B1 (en) * | 1983-03-11 | 1990-11-22 | FUJIREBIO KABUSHIKI KAISHA also trading as FUJIREBIO INC. | Method of measuring ligands |
IT1199088B (it) * | 1984-03-09 | 1988-12-30 | Miles Italiana | Saggio di legame specifico mediante impiego di anti-g6pdh come marcante |
US4622294A (en) * | 1985-02-08 | 1986-11-11 | Kung Viola T | Liposome immunoassay reagent and method |
US5068198A (en) * | 1986-03-26 | 1991-11-26 | Syntex (U.S.A.) Inc. | Liquid single reagent for assays involving confining gels |
EP0399127A1 (en) * | 1989-05-23 | 1990-11-28 | Pharmacia ENI Diagnostics Inc. | Homogeneous immunochemical method for determining haptens by means of ion selective electrodes |
DE3919915A1 (de) * | 1989-06-19 | 1990-12-20 | Boehringer Mannheim Gmbh | Aminoalkylmaleimide und davon abgeleitete hapten- und antigenderivate sowie konjugate mit peptiden oder proteinen |
JPH0833394B2 (ja) * | 1990-10-03 | 1996-03-29 | 三洋化成工業株式会社 | 酵素標識ハプテンの製法 |
DK0487301T3 (da) * | 1990-11-20 | 2000-09-18 | Dade Behring Marburg Gmbh | Fremgangsmåde til stabilisering af enzymkonjugater |
DE69121844T2 (de) * | 1990-11-20 | 1997-01-23 | Behringwerke Ag | Immunotest für Cyclosporin |
CA2087397A1 (en) * | 1992-01-22 | 1993-07-23 | Kazuhisa Kubotsu | Immunoassay and reagents used therefor |
CA2156397C (en) * | 1993-04-08 | 2007-05-15 | Valerie Quesniaux | Rapamycin assay |
US6455288B1 (en) * | 1993-04-08 | 2002-09-24 | Dade Behring Marburg Gmbh | Homogeneous immunoassays using mutant glucose-6-phosphate dehydrogenases |
US5747352A (en) * | 1994-05-23 | 1998-05-05 | Beckman Instruments, Inc. | Reagents and methods for the rapid and quantitative assay of pharmacological agents |
CN1319105A (zh) * | 1998-10-09 | 2001-10-24 | 伊索技术公司 | 制备针对环孢菌素及其代谢物特异性区域的抗体的方法 |
AUPP751398A0 (en) * | 1998-12-04 | 1999-01-07 | Commonwealth Scientific And Industrial Research Organisation | Methotrexate derivatives |
US7078495B1 (en) * | 1999-08-03 | 2006-07-18 | Dade Behring Inc. | Monoclonal antibodies to tacrolimus and immunoassay methods for tacrolimus |
US6653456B2 (en) * | 2001-07-31 | 2003-11-25 | Roche Diagnostics Corporation | Site-specific aminoglycoside derivatives and their use in immunodiagnostic assays |
US20050176080A1 (en) * | 2004-02-10 | 2005-08-11 | Vani Bodepudi | Hapten, immunogens and derivatives of ascomycin useful for preparation of antibodies and immunoassays |
US20060046273A1 (en) * | 2004-08-27 | 2006-03-02 | Lin-Zhi International Inc. | Homogeneous enzyme immunoassay for oral fluid |
BRPI0517207A (pt) * | 2004-12-17 | 2008-09-30 | Isotechnika Inc | composto isolado, metabólito isolado de ciclo {{(e)- e (z)- (2s,3r,4r)-3-hidróxi-4-metil-2-(metilamino)-6,8-nonadien oil}-l-2-aminobutiril-n-metil-glicil-n-metil-l-leucil-l-v alil-n-metil-l-leucil-l-alanil-d-alanil-n-metil-l-leucil- n-metil-l-leucil-n-metil-l-valil} (isa247) e os sais e solvatos farmaceuticamente aceitáveis dos mesmos, método de preparação de metabólitos de isa247 in vitro, método de produção de um metabólito hidroxilado de isa247, metabólito hidroxilado isolado de isa247, metabólito hidroxilado isolado, método de produção de um metabólito de epóxido de isa247 in vitro, metabólito isolado de epóxido de isa247, metabólito isolado de epóxido, método de produção de um metabólito de diol de isa247 in vitro, metabólito de diol isolado de isa247, metabólito de diol isolado, método de produção de um metabólito de diol de isa247, método de produção de um metabólito de diol de isa247 e composição farmacêutica |
US7189582B2 (en) * | 2005-04-27 | 2007-03-13 | Dade Behring Inc. | Compositions and methods for detection of sirolimus |
JP4746926B2 (ja) * | 2005-06-29 | 2011-08-10 | シスメックス株式会社 | グルコース−6−リン酸脱水素酵素含有試薬及びグルコース−6−リン酸脱水素酵素安定化方法 |
CN101638640B (zh) * | 2009-09-07 | 2011-01-12 | 北京利德曼生化股份有限公司 | 葡萄糖-6-磷酸脱氢酶及其核苷酸序列、重组载体、重组宿主细胞和试剂盒 |
JP2014503197A (ja) * | 2010-11-24 | 2014-02-13 | ディーエイチ テクノロジーズ デベロップメント プライベート リミテッド | グルコース−6−リン酸脱水素酵素のハイスループット、高感度の検出 |
CN102565399B (zh) * | 2010-12-07 | 2015-06-03 | 北京望尔生物技术有限公司 | 一种检测氢化可的松的方法及其专用酶联免疫试剂盒 |
CN102807618A (zh) * | 2011-08-10 | 2012-12-05 | 重庆金域医学检验所有限公司 | 苯妥因均相酶免疫检测试剂盒及其多克隆抗体的制备方法 |
JP5896375B2 (ja) * | 2011-09-09 | 2016-03-30 | 池田食研株式会社 | 改変型グルコース脱水素酵素遺伝子 |
CN102424829B (zh) * | 2011-10-26 | 2013-10-16 | 苏州汉酶生物技术有限公司 | 一种酶催化合成坦西莫司的方法 |
US8771964B2 (en) * | 2012-02-02 | 2014-07-08 | Siemens Healthcare Diagnostics Inc. | Compositions and methods for detection of methadone metabolite |
KR20150023729A (ko) * | 2012-06-14 | 2015-03-05 | 암브룩스, 인코포레이티드 | 핵 수용체 리간드 폴리펩티드에 접합된 항-psma 항체 |
CN103242446A (zh) * | 2012-07-25 | 2013-08-14 | 苏州博源医疗科技有限公司 | 茶碱免疫原及其制备方法和应用 |
CN102757391B (zh) * | 2012-08-01 | 2015-08-26 | 苏州博源医疗科技有限公司 | 一种***衍生物及其制备方法和应用 |
WO2015094852A2 (en) * | 2013-12-17 | 2015-06-25 | Siemens Healthcare Diagnostics Inc. | Preparation of multi-hapten mutant g6pdh conjugates and their use for detection of multiple analytes |
CN104016923B (zh) * | 2014-01-08 | 2016-08-31 | 南开大学 | 苯妥英衍生物及其制备方法和用途 |
CN103760348B (zh) * | 2014-02-11 | 2015-03-11 | 苏州博源医疗科技有限公司 | 一种甘胆酸免疫检测试剂及其制备和检测方法 |
CN103739703B (zh) * | 2014-02-11 | 2015-07-15 | 苏州博源医疗科技有限公司 | 甘胆酸免疫原、抗甘胆酸特异性抗体及检测试剂 |
JP6398295B2 (ja) * | 2014-04-30 | 2018-10-03 | ニプロ株式会社 | 変異型グルコース−6−リン酸脱水素酵素 |
CN104447745B (zh) * | 2014-11-06 | 2016-03-30 | 济南金域医学检验中心有限公司 | 一种茶碱均相酶免疫检测验试剂盒及其制备方法 |
CN104569373B (zh) * | 2015-01-27 | 2016-08-17 | 苏州博源医疗科技有限公司 | 一种甲氨蝶呤均相酶免疫检测试剂及其制备和检测方法 |
CN107636170A (zh) * | 2015-02-04 | 2018-01-26 | 健泰科生物技术公司 | 突变型Smoothened及其使用方法 |
CN105131105A (zh) * | 2015-07-27 | 2015-12-09 | 苏州博源医疗科技有限公司 | 皮质醇免疫原、衍生物、抗体、检测试剂及制备方法 |
CN106565809B (zh) * | 2016-07-08 | 2018-05-01 | 北京九强生物技术股份有限公司 | 一种β半乳糖苷酶的酶供体偶联物及其在甘胆酸检测中的用途 |
CN106226512B (zh) * | 2016-07-29 | 2018-10-16 | 胡清 | 一种试剂盒、试剂盒的制备方法及利用该试剂盒实现的外周血甘氨胆酸的检测方法 |
CN106190996B (zh) * | 2016-08-30 | 2019-05-21 | 美康生物科技股份有限公司 | 一种葡萄糖6磷酸脱氢酶突变体 |
CN109797143B (zh) * | 2016-09-22 | 2021-02-12 | 北京九强生物技术股份有限公司 | 一种包含大肠杆菌β半乳糖苷酶受体的试剂 |
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