400-998-5282
专注多肽 服务科研
400-998-5282
专注多肽 服务科研
NOTA-P2-RM26 是一种拮抗性 Bombesin 类似物，胃泌素释放肽受体 (GRPR/ BB2) 是前列腺癌可视化的分子靶点。NOTA-P2-RM26 用 111In 和 68Ga 标记后可用于 PET 和 SPECT/CT 进行前列腺癌成像的研究。
编号：179063
CAS号：1446005-10-2
单字母：NOTA-PEG2-CH2CO-fQWAVGHSta-L-CONH2
NOTA-P2-RM26 是一种拮抗性 Bombesin 类似物，胃泌素释放肽受体 (GRPR/ BB2) 是前列腺癌可视化的分子靶点。NOTA-P2-RM26 用 111In 和 68Ga 标记后可用于 PET 和 SPECT/CT 进行前列腺癌成像的研究。
胃泌素释放肽受体（GRPR/BB2）是前列腺癌显像的分子靶点。研究致力于开发用于PET和SPECT的高亲和力、亲水性、拮抗性蛙皮素类显像剂。研究人员合成了蛙皮素拮抗剂类似物D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2（[D-Phe6,Sta13,Leu14]-蛙皮素[6-14]），并通过二甘醇（PEG2）连接子将其与1,4,7-三氮杂环壬烷-N,N',N''-三乙酸（NOTA）偶联。所得偶联物NOTA-PEG2-[D-Phe6,Sta13,Leu14]蛙皮素[6-14]（NOTA-P2-RM26）分别用68Ga（半衰期68分钟，正电子发射体）和111In（半衰期2.8天，γ发射体）进行标记。
研究考察了两种标记化合物的标记稳定性、特异性、抑制效率（IC50）和解离常数（KD），以及它们的细胞滞留和内化情况。同时还在正常NMRI小鼠和PC-3肿瘤Balb/c nu/nu小鼠中研究了双同位素（111In/68Ga）标记肽的药代动力学。NOTA-P2-RM26的111In和68Ga标记放射化学产率均>98%。两种偶联物均显示出对GRPR的高特异性和结合亲和力，其中111In标记化合物在饱和结合实验中的KD值为23±13 pM。在竞争性结合实验中，natIn-和natGa-NOTA-P2-RM26显示出低纳摩尔水平的结合抑制浓度（IC50分别为1.24±0.29 nM和0.91±0.19 nM）。放射性标记偶联物的内化速率较慢。
在正常小鼠中，放射性金属标记示踪剂通过肾脏快速清除血液，并在胰腺中呈现GRPR特异性摄取。对PC-3异种移植小鼠的肿瘤靶向和生物分布研究表明，仅注射45 pmol肽1小时后，肿瘤即显示出高特异性摄取（68Ga为8.1±0.4%ID/g，111In为5.7±0.3%ID/g）和高肿瘤背景比（肿瘤/血液：68Ga为12±1，111In为10±1）。注射后短时间内即可通过γ相机和微型PET相机观察到异种移植瘤。研究表明，拮抗性蛙皮素类似物NOTA-PEG2-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2（NOTA-P2-RM26）是用于PET和SPECT/CT前列腺癌成像的理想候选药物。
参考文献
https://doi.org/10.1021/bc300659k
Definition
Bombesin is a polypeptide that is found in the brain and gastrointestinal tract. Experimentally it has shown to cause the secretion of various substances (as gastrin and cholecystokinin) and to inhibit intestinal motility.
Discovery
Bombesin was isolated from the skin of the frog Bombina bonmina by Anastasi and team in 19711.
Classification
Bombesin-like peptides are grouped into three families - 1) Bombesin group, viz., bombesin and alytesin, 2) Ranatensin group viz., ranatensins, litorin, and Rohdei litorin, 3) Phyllolitorin group viz., Leu(8)- and Phe(8)-phyllolitorins.
Structural characteristics
Bombesin is a small peptide of 14 amino acids.
Mode of action
The biological activity of bombesin is mediated by binding to specific receptors viz., gastrin releasing peptide receptor (GRPR; called also BB2 receptor), neuromedin B receptor (NMBR; called also BB1 receptor) and bombesin receptor subtype 3 (BRS-3; called also BB3 receptor). Bombesin induce Ca2+ release from intracellular stores2.
Functions
Bombesin and bombesin-like factors show a wide spectrum of biological activities. It regulates the contraction of smooth muscle cells, induction of the secretion of neuropeptides and hormones. It is one of the most powerful substances showing anorexic effects in the hypothalamus. It induces the release of gastrin and cholecystokinin in the intestines and the pancreas. They also posses activities of cytokines.
References
1. Anastasi A, Erspamer V, Bucci M (1971). Isolation and structure of bombesin and alytesin, 2 analogous active peptides from the skin of the European amphibians Bombina and Alytes. Experientia., 27(2):166-167.
2. Wang JL, Kalyanaraman S, Vivo MD, Gautam N (1996). Bombesin and thrombin affect discrete pools of intracellular calcium through different G-proteins. Biochem J., 320:87-91.
很多蛋白在细胞中非常容易被降解，或被标记，进而被选择性地破坏。但含有部分D型氨基酸的多肽则显示了很强的抵抗蛋白酶降解能力。
【拮抗剂多肽在癌症治疗中的作用机制】
1 、抑制肿瘤细胞增殖：某些多肽能够直接作用于肿瘤细胞，干扰其增殖信号传导路径，从而抑制肿瘤细胞的增长。
2 、诱导肿瘤细胞凋亡：多肽可以通过模拟肿瘤抑制蛋白或激活凋亡信号通路，促进肿瘤细胞走向程序性死亡。
3 、免疫调节：多肽类化合物能够激活机体的免疫系统，增强免疫细胞对肿瘤细胞的识别和攻击能力，从而辅助控制肿瘤生长。
4、阻断蛋白质相互作用：多肽可以设计成特定的结构，以阻断肿瘤细胞内部或肿瘤微环境中关键蛋白质的相互作用，这些相互作用对于肿瘤的生存和扩散至关重要。
5、抑制肿瘤新生血管生成：多肽通过抑制血管内皮生长因子（VEGF）等促进血管生成的因子，切断肿瘤的血液供应，抑制肿瘤生长和转移。
6 、靶向递送：多肽可以通过与其表面受体特异性结合，实现对肿瘤细胞的靶向递送，提高药物的疗效并减少对正常细胞的毒性。
NOTA修饰肽的说明:
2,2′,2”-(1,4,7-triazacyclononane-1,4,7-triyl)triacetic acid (NOTA) is a metal chelator used as a complexing agent for metal ions. Its complexes have applications as contrast agents and cancer treatments.
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