【技术实现步骤摘要】
一.
目前癌症仍然是严重威胁人类健康的疾病,发病率和死亡率都很高。癌症的传统治疗方法主要有3种方法化疗,放疗和手术治疗。手术疗法仅限于早期,而化疗和放疗虽然有效,但是其严重的毒副作用限制了这种方法不能使用大剂量和长期应用,从而大大影响了其治疗效果。 因此,现阶段人们致力于研究一种低毒高效治疗肿瘤的新方法,就是消除放、化疗方法在杀伤肿瘤细胞的同时也大量杀伤正常细胞的缺点,特异性地针对肿瘤细胞进行杀伤,而对正常细胞低毒性或没有毒性。这种方法就是应用靶向分子,包括肿瘤细胞表面过量表达的受体的配体和单克隆抗体等,这种靶向分子进入体内可以特异性地到达肿瘤部位,而与其相连的效应蛋白或与其偶联的化疗药物可以在肿瘤部位杀伤肿瘤细胞,从而达到特异性治疗肿瘤的目的。 但是,由于该类融合蛋白只对表达靶向分子受体的癌细胞起作用,使得在给药前能清楚了解目的癌细胞是否表达靶向分子受体,变得非常重要。这样可以大大提高治疗效果,避免耽误无关病人的治疗。 二.
技术介绍
靶向性药物的研究是癌症治疗的一大进步,目前,人们发现约40%的癌细胞表面特异性表达GnRH受体,故而针对性研究以GnRH靶向物的靶向融合蛋白,去特异性的杀死癌细胞,具有跨时代的意义。然而,在用该类药物治疗前,能明确知道病人所患的癌症是否表达GnRH受体,就变得尤为重要。使得该类药物的靶向性效果更强.此类靶向药物基本结构为导向部分通常连接一个毒素蛋白,如假单胞菌外毒素(PE),白喉毒素(DT),蓖麻毒素等,现在较常用的是假单胞菌外毒素A(PE),PE是由假单胞杆菌分泌的,由613个氨基酸组成,其分为3个区域,I区为 ...
【技术保护点】
一类能与表达GnRH受体的癌细胞特异结合且用锝-99m标记的蛋白,此类蛋白主要用于对表达GnRH受体的癌细胞,在人体内的检测及定位。其特征为:被锝-99m标记的这类蛋白一定包含有GnRH或者GnRH突变体的氨基酸序列。
【技术特征摘要】
1.一类能与表达GnRH受体的癌细胞特异结合且用锝-99m标记的蛋白,此类蛋白主要用于对表达GnRH受体的癌细胞,在人体内的检测及定位。其特征为被锝-99m标记的这类蛋白一定包含有GnRH或者GnRH突变体的氨基酸序列。2.如权力要求1所述,GnRH及其突变体的氨基酸序列如下Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly,其突变体为第六位的Gly(甘氨酸)被Lys(赖氨酸),D-Lys,Ala(丙氨酸),ornithine(鸟氨酸),D-ornithine,Glu(谷氨酸),D-Glu,Asp(天冬氨酸),D-Asp,Cys(半胱氨酸),D-Cys,Tyr(酪氨酸)和D-Tyr3.如权力要求2所述,GnRH氨基酸序列的N末端多加一个蛋氨酸(Met),使得该序列变为11个氨基酸。4.GnRH-PE融合蛋白在组成结构上,GnRH与PE之间可以直接相连,也可以通过一段Linker相连。5.如权力要求1,2,3所述,在GnRH及其突变体与PE40蛋白形成融合蛋白,该序列被锝-99m标记.Met-Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-His-Met-Ala-Glu-Glu-Gly-Gly-Ser-Leu-Ala-Ala-Leu-Thr-Ala-His-Gln-Ala-Cys-His-Leu-Pro-Leu-Glu-Thr-Phe-Thr-Arg-His-Arg-Gln-Pro-Arg-Gly-Trp-Glu-Gln-Leu-Glu-Gln-Cys-Gly-Tyr-Pro-Val-Gln-Arg-Leu-Val-Ala-Leu-Tyr-Leu-Ala-Ala-Arg-Leu-Ser-Trp-Asn-Gln-Val-Asp-Gln-Val-Ile-Arg-Asn-Ala-Leu-Ala-Ser-Pro-Gly-Ser-Gly-Gly-Asp-Leu-Gly-Glu-Ala-Ile-Arg-Glu-Gln-Pro-Glu-Gln-Ala-Arg-Leu-Ala-Leu-Thr-Leu-Ala-Ala-Ala-Glu-Ser-Glu-Arg-Phe-Val-Arg-Gln-Gly-Thr-Gly-Asn-Asp-Glu-Ala-Gly-Ala-Ala-Asn-Ala-Asp-Val-Val-Ser-Leu-Thr-Cys-Pro-Val-Ala-Ala-Gly-Glu-Cys-Ala-Gly-Pro-Ala-Asp-Ser-Gly-Asp-Ala-Leu-Leu-Glu-Arg-Asn-Tyr-Pro-Thr-Gly-Ala-Glu-Phe-Leu-Gly-Asp-Gly-Gly-Asp-Val-Ser-Phe-Ser-Thr-Arg-Gly-Thr-Gln-Asn-Trp-Thr-Val-Glu-Arg-Leu-Leu-Gln-Ala-His-Arg-Gln-Leu-Glu-Glu-Arg-Gly-TyrVal-Phe-Val-Gly-Tyr-His-Gly-Thr-Phe-Leu-Glu-Ala-Ala-Gln-Ser-Ile-Val-Phe-Gly-Gly-Val-Arg-Ala-Arg-Ser-Gln-Asp-Leu-Asp-Ala-Ile-Trp-Arg-Gly-Phe-Tyr-Ile-Ala-Gly-Asp-Pro-Ala-Leu-Ala-Tyr-Gly-Tyr-Ala-Gln-Asp-Gln-Glu-Pro-Asp-Ala-Arg-Gly-Arg-Ile-Arg-Asn-Gly-Ala-Leu-Leu-Arg-Val-Tyr-Val-Pro-Arg-Ser-Ser-Leu-Pro-Gly-Phe-Tyr-Arg-Thr-Ser-Leu-Thr-Leu-Ala-Ala-Pro-Glu-Ala-Ala-Gly-Glu-Val-Glu-Arg-Leu-Ile-Gly-His-Pro-Leu-Pro-Leu-Arg-Leu-Asp-Ala-Ile-Thr-Gly-Pro-Glu-Glu-Glu-Gly-Gly-Arg-Leu-Glu-Thr-Ile-Leu-Gly-Trp-Pro-Leu-Ala-Glu-Arg-Thr-Val-Val-Ile-Pro-Ser-Ala-Ile-Pro-Thr-Asp-Pro-Arg-Asn-Val-Gly-Gly-Asp-Leu-Asp-Pro-Ser-Ser-Ile-Pro-Asp-Lys-Glu-Gln-Ala-Ile-Ser-Ala-Leu-Pro-Asp-Tyr-Ala-Ser-Gln-Pro-Gly-Lys-Pro-Pro-Arg-Glu-Asp-Leu-Lys6.根据权利要求1,2,3所述,在GnRH及其突变体与PE40突变体蛋白形成融合蛋白,该序列被锝-99m标记Met-Glu-His-Trp-Ser-Tyr-Ala-Leu-Arg-Pro-Gly-His-Met-Ala-Glu-Glu-Gly-Gly-Ser-Leu-Ala-Ala-Leu-Thr-Ala-His-Gln-Ala-Cys-His-Leu-Pro-Leu-Glu-Thr-Phe-Thr-Arg-His-Arg-Gln-Pro-Arg-Gly-Trp-Glu-Gln-Leu-Glu-Gln-Cys-Gly-Tyr-Pro-Val-Gln-Arg-Leu-Val-Ala-Leu-Iyr-Leu-Ala-Ala-Arg-Leu-Ser-Trp-Asn-Gln-Val-Asp-Gln-Val-Ile-Arg-Asn-Ala-Leu-Ala-Ser-Pro-Gly-Ser-Gly-Gly-Asp-Leu-Gly-Glu-Ala-Ile-Arg-Glu-Gln-Pro-Glu-Gln-Ala-Arg-Leu-Ala-Leu-Thr-Leu-Ala-Ala-Ala-Glu-Ser-Glu-Arg-Phe-Val-Arg-Gln-Gly-Thr-Gly-Asn-Asp-Glu-Ala-Gly-Ala-Ala-Asn-Ala-Asp-Val-Val-Ser-Leu-Thr-Cys-Pro-Val-Ala-Ala-Gly-Glu-Cys-Ala-Gly-Pro-Ala-Asp-Ser-Gly-Asp-Ala-Leu-Leu-Glu-Arg-Asn-Tyr-Pro-Thr-Gly-Ala-Glu-Phe-Leu-Gly-Asp-Gly-Gly-Asp-Val-Ser-Phe-Ser-Thr-Arg-Gly-Thr-Gln-Asn-Trp-Thr-Val-Glu-Arg-Leu-Leu-Gln-Ala-His-Arg-Gln-Leu-Glu-Glu-Arg-Gly-Tyr-Val-Phe-Val-Gly-Tyr-His-Gly-Thr-Phe-Leu-Glu-Ala-Ala-Gln-Ser-Ile-Val-Phe-Gly-Gly-Val-Arg-Ala-Arg-Ser-Gln-Asp-Leu-Asp-Ala-Ile-Trp-Arg-Gly-Phe-Tyr-Ile-Ala-Gly-Asp-Pro-Ala-Leu-Ala-Tyr-Gly-Tyr-Ala-Gln-Asp-Gln-Glu-Pro-Asp-Ala-Arg-Gly-Arg-Ile-Arg-Asn-Gly-Ala-Leu-Leu-Arg-Val-Tyr-Val-Pro-Arg-Ser-Ser-Leu-Pro-Gly-Phe-Tyr-Arg-Thr-Ser-Leu-Thr-Leu-Ala-Ala-Pro-Glu-Ala-Ala-Gly-Glu-Val-Glu-Arg-Leu-Ile-Gly-His-Pro-Leu-Pro-Leu-Arg-Leu-Asp-Ala-Ile-Thr-Gly-Pro-Glu-Glu-Glu-Gly-Gly-Arg-Leu-Glu-Thr-Ile-Leu-Gly-Trp-Pro-Leu-Ala-Glu-Arg-Thr-Val-Val-Ile-Pro-Ser-Ala-Ile-Pro-Thr-Asp-Pro-Arg-Asn-Val-Gly-Gly-Asp-Leu-Asp-Pro-Ser-Ser-Ile-Pro-Asp-Lys-Glu-Gln-Ala-Ile-Ser-Ala-Leu-Pro-Asp-Tyr-Ala-Ser-Gln-Pro-Gly-Lys-Pro-Pro-Lys-Asp-Glu-Leu7.根据权利要求1,2,3所述,在GnRH及其突变体与PE38突变体蛋白形成融合蛋白,该序列被锝-99m标记Met-Glu-His-Trp-Ser-Tyr-Ala-Leu-Arg-Pro-Gly-His-Met-Ala-Glu-Glu-Gly-Gly-Ser-Leu-Ala-Ala-Leu-Thr-Ala-His-Gln-Ala-Cys-His-Leu-Pro-Leu-Glu-Thr-Phe-Thr-Arg-His-Arg-Gln-Pro-Arg-Gly-Trp-Glu-Gln-Leu-Glu-Gln-Cys-Gly-Tyr-Pro-Val-Gln-Arg-Leu-Val-Ala-Leu-Tyr-Leu-Ala-Ala-Arg-Leu-Ser-Trp-Asn-Gln-Val-Asp-Gln-Val-Ile-Arg-Asn-Ala-Leu-Ala-Ser-Pro-Gly-Ser-Gly-Gly-Asp-Leu-Gly-Glu-Ala-Ile-Arg-Glu-Gln-Pro-Glu-Gln-Ala-Arg-Leu-Ala-Leu-Thr-Leu-Ala-Ala-Ala-Glu-Ser-Glu-Arg-Phe-Val-Arg-Gln-Gly-Thr-Gly-Asn-Asp-Glu-Ala-GIy-Ala-Ala-Asn-Gly-Pro-Ala-Asp-Ser-Gly-Asp-Ala-Leu-Leu-Glu-Arg-Asn-Tyr-Pro-Thr-Gly-Ala-Glu-Phe-Leu-Gly-Asp-Gly-Gly-Asp-Val-Ser-Phe-Ser-Thr-Arg-Gly-Thr-Gln-Asn-Trp-Thr-Val-Glu-Arg-Leu-Leu-Gln-Ala-His-Arg-Gln-Leu-Glu-Glu-Arg-Gly-Tyr-Val-Phe-Val-Gly-Tyr-His-Gly-Thr-Phe-Leu-Glu-Ala-Ala-Gln-Ser-Ile-Val-Phe-Gly-Gly-Val-Arg-Ala-Arg-Ser-Gln-Asp-Leu-Asp-Ala-Ile-Trp-Arg-Gly-Phe-Tyr-Ile-Ala-Gly-Asp-Pro-Ala-Leu-Ala-Tyr-Gly-Tyr-Ala-Gln-Asp-Gln-Glu-Pro-Asp-Ala-Arg-Gly-Arg-Ile-Arg-Asn-Gly-Ala-Leu-Leu-Arg-Val-Tyr-Val-Pro-Arg-Ser-Ser-Leu-Pro-Gly-Phe-Tyr-Arg-Thr-Ser-Leu-Thr-Leu-Ala-Ala-Pro-Glu-Ala-Ala-Gly-Glu-Val-Glu-Arg-Leu-Ile-Gly-His-Pro-Leu-Pro-Leu-Arg-Leu-Asp-Ala...
【专利技术属性】
技术研发人员:金美玉,马素永,聂李亚,许日山,
申请(专利权)人:北京诺思兰德生物技术有限责任公司,
类型:发明
国别省市:11[中国|北京]
还没有人留言评论。发表了对其他浏览者有用的留言会获得科技券。