The invention discloses an anti-tumor polypeptide, which is a computer-aided design and synthesized polypeptide composed of 81 amino acids. In the optimization process of the anti-cancer polypeptide, not only the conventional polypeptide design strategy of selective substitution and addition and deletion of amino acids is adopted, but also the side chain reconstruction strategy of amino acids is integrated into the design concept. To a greater extent, the ideal polypeptide structure is obtained. The anti-tumor polypeptide chain of the invention is short and can be obtained by solid-phase synthesis by conventional Fmoc method. It is an inhibitor of PD 1 and has good inhibitory activity against tumors. Monoclonal antibodies and ELISA kits were further obtained on the basis of anti-tumor polypeptide, which were used to detect the content of anti-tumor polypeptide in blood during drug development.
【技术实现步骤摘要】
一种抗肿瘤多肽及其单克隆抗体和ELISA试剂盒
本专利技术属于多肽设计与固相合成、抗体制备与检测和药理活性研究领域,具体涉及一种抗肿瘤多肽及其单克隆抗体和ELISA试剂盒。技术背景恶性肿瘤是一种严重损害人类健康的疾病,我国肿瘤造成的死亡占全部死亡的四分之一。据统计,2011年全国每10万人中就有250人患恶性肿瘤。近几十年,我国恶性肿瘤的发病率每年都有提高,发病率的上升趋势趋向于直线。据估计,在2049年我国每10万人中将有400人患癌症。目前肿瘤的治疗手段在很大程度上仍是以药物治疗为主。因而,研究以及开发新型的高效、低毒抗肿瘤药物具有非常重要的意义。其中,氨基酸导向的小肽化合物具有非常好的抗肿瘤活性。除此之外,氨基酸载体具备非常好的生物亲和性和生物相容性。在一些抗肿瘤药物分子中,引入氨基酸,能够提高药物的选择性和生物相容性,并且能降低其对正常细胞的毒性。另一方面,肽类是全能型的生物活性分子之一,假肽和伪肽类化合物以及其衍生物的生物活性非常多,例如抗菌,抗病毒和抗癌等活性。机体T细胞免疫在控制肿瘤的发生、发展过程中起到了重要作用。其中肿瘤局部浸润性CD8+T淋巴细胞在机体抗肿瘤免疫应答中发挥了关键作用。近年来发现,肿瘤患者体内存在免疫抑制机制,妨碍机体对肿瘤的清除,导致肿瘤长期定植,表现为T淋巴细胞功能障碍与增殖能力减弱。PD-1已被公认为是衰竭性T淋巴细胞的表面标志。阻断PD-1/PD-L1通路可以部分恢复衰竭性T细胞的功能。已知PD-1(programmeddeath1)程序性死亡受体1,是一种重要的免疫抑制分子。以PD-1为靶点的免疫调节对抗肿瘤 ...
【技术保护点】
1.一种抗肿瘤多肽,其序列如SEQ ID NO:1所示。
【技术特征摘要】
1.一种抗肿瘤多肽,其序列如SEQIDNO:1所示。2.如权利要求1所述的抗肿瘤多肽,其特征是,序列中第17位的氨基酸Tyr、第46位的氨基酸Phe、第77位的氨基酸Tyr至少有一个替换为。3.如权利要求2所述的抗肿瘤多肽,选自:Ser-Val-Phe-Trp-Lys-Gly-Gly-Arg-Glu-His-His-Asp-Lys-His-Leu-Ala-Baa-Ile-Arg-Phe-His-Trp-Asn-Glu-Leu-Tyr-Glu-Asn-Asp-Ile-Pro-Gly-Ser-Gly-Pro-Phe-Asn-Asn-Ala-Gly-Ser-Leu-Gln-Gly-Ser-Phe-Ile-Asn-Glu-Trp-Asn-Arg-Leu-Gly-Lys-Ile-Gly-Thr-Ala-Met-Arg-Asp-Phe-Leu-Thr-Tyr-Ala-Pro-Pro-Thr-Asp-Trp-Ile-Leu-Cys-Asn-Tyr-Ile-Gly-Thr-Ala;Ser-Val-Phe-Trp-Lys-Gly-Gly-Arg-Glu-His-His-Asp-Lys-His-Leu-Ala-Tyr-Ile-Arg-Phe-His-Trp-Asn-Glu-Leu-Tyr-Glu-Asn-Asp-Ile-Pro-Gly-Ser-Gly-Pro-Phe-Asn-Asn-Ala-Gly-Ser-Leu-Gln-Gly-Ser-Baa-Ile-Asn-Glu-Trp-Asn-Arg-Leu-Gly-Lys-Ile-Gly-Thr-Ala-Met-Arg-Asp-Phe-Leu-Thr-Tyr-Ala-Pro-Pro-Thr-Asp-Trp-Ile-Leu-Cys-Asn-Tyr-Ile-Gly-Thr-Ala;Ser-Val-Phe-Trp-Lys-Gly-Gly-Arg-Glu-His-His-Asp-Lys-His-Leu-Ala-Tyr-Ile-Arg-Phe-His-Trp-Asn-Glu-Leu-Tyr-Glu-Asn-Asp-Ile-Pro-Gly-Ser-Gly-Pro-Phe-Asn-Asn-Ala-Gly-Ser-Leu-Gln-Gly-Ser-Phe-Ile-Asn-Glu-Trp-Asn-Arg-Leu-Gly-Lys-Ile-Gly-Thr-Ala-Met-Arg-Asp-Phe-Leu-Thr-Tyr-Ala-Pro-Pro-Thr-Asp-Trp-Ile-Leu-Cys-Asn-Baa-Ile-Gly-Thr-Ala;Ser-Val-Phe-Trp-Lys-Gly-Gly-Arg-Glu-His-His-Asp-Lys-His-Leu-Ala-Baa-Ile-Arg-Phe-His-Trp-Asn-Glu-Leu-Tyr-Glu-Asn-Asp-Ile-Pro-Gly-Ser-Gly-Pro-Phe-Asn-Asn-Ala-Gly-...
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