GE11 多肽

H-YHWYGYTPQNVI-OH

H-Tyr-His-Trp-Tyr-Gly-Tyr-Thr-Pro-Gln-Asn-Val-Ile-OH

12

95.2

C₇₅H₉₇N₁₇O₁₉

1540.67

固相合成

EGFR is a crucial driver of tumorigenesis abundantly overexpressed, amplified or mutated in many cancers including lung and breast cancers, and glioblastomas. EGFR overexpression or mutation often correlate with drug resistance thereby presenting EGFR as a possible target in many malignant tumors. For the identification of EGFR binding peptides, T7 phage displayed peptide library was incubated with the purified human EGFR. After three rounds of panning, the dodecapeptide termed GE11 (YHWYGYTPQNVI) was shown to bind specifically to EGFR. The peptide showed high binding affinity in nanomolar range (KD = approximately 22 nM) that could be inhibited by EGF, indicating that they bound to the same site on EGFR. In vivo targeting ability of the radioactively labeled 125I-GE11 peptide was validated after intravenous (i.v.) infusion of the conjugate into nude mice bearing subcutaneous hepatocellular carcinoma (SMMC-7721) xenografts. The tumor targeting of 125I-GE11 was inhibited by a 100-fold excess of cold GE11 peptide. In addition, GE11 peptide was used as a gene delivery vehicle upon conjugation to the polyethylenimine (PEI) polyplexes using a glycine (G-G-G-S) linker system and intravenously administered to the SMMC-7721 bearing mice. Cheng and colleagues reported the conjugation of GE11 to Doxil for targeted in vivo delivery to EGFR-overexpressing non-small cell lung cancer (A549). Doxil (PEGylated liposomal Dox, PEG-LP/Dox, or non-PEGylated Dox, LP/Dox) is an FDA approved chemotherapy comprising doxorubicin drug encapsulated in liposomes. Doxil, also referred to as Lipo-Dox, is widely used in the clinics for ovarian cancer treatment. Very promising results were obtained when the GE11-conjugated doxorubicin filled liposomes (GE11-PS-Dox) were used to treat ovarian cancer xenograft bearing mice, indicating GE11-guided drug targeting as an alternative for treatment of EGFR overexpressing ovarian cancers. GE11-PS-Dox treatment very significantly increased the survival rate with minimal toxicity compared to non-targeting control (PS-Dox) or the clinically used Lipo-Dox. In a similar fashion, GE11-PS-Dox also showed prolonged survival compared to the PBS- and non-targeting treatment controls (PS-Dox, Lipo-Dox) in a preclinical liver cancer treatment study. Moreover, several GE11-targeted radionuclides have been studied in imaging of EGFR overexpressing tumors with either PET or SPECT.

一般情况下， GE11 多肽 粉末应该保存在-20甚至-70摄氏度. GE11 多肽 溶解后应该-70摄氏度分装保存，避免反复冻融. 了解更多细节，请查阅手册:多肽溶解及保存指南

• Li Z, Zhao R, Wu X, Sun Y, Yao M, Li J, et al. Identification and characterization of a novel peptide ligand of epidermal growth factor receptor for targeted delivery of therapeutics. FASEB J. 2005;19(14):1978-85

三氟乙酸（TFA）是一种强酸，常用于从固相树脂中裂解合成的多肽，也可用于提高多肽纯化步骤中的HPLC性能。默认情况下，定制的多肽是以冻干的TFA盐的形式交付的，其中TFA的含量可能高达10-45%。

定制多肽中的TFA可能会导致后续检测数据出现无法解释的差异。例如，nM浓度的TFA已被证明会干扰细胞实验，在某些情况下会抑制细胞增殖，而在其他情况下会增加细胞活力。

TFA去除服务推荐用于:

• 将用于细胞试验的多肽
• 将被用作原料药或制成品的多肽
• 含有大量碱性残基的亲水多肽

干品多肽的重量中不仅仅包含多肽，还包含有一些非肽的组份，如水、被吸收的溶剂、配位离子和盐等。肽的净含量是指肽在其中的重量百分比，这个百分比的数值范围很大，可能从50%到90%，取决于纯度、序列以及合成和纯化的方法，不要将肽的净含量和肽的纯度混为一谈，他们是两个完全不同的概念。纯度通常是通过HPLC测定的。纯度定义的是多肽样品中含正确序列的组分的百分比，而肽的净含量是指样品中肽类物质相对于总物质所占的百分比，肽的净含量通常是氨基酸组分分析或紫外分光法测定的，这个信息主要是在一些对肽的浓度很敏感的实验中，对计算肽的浓度是很重要的。