Sequence 3 letters:

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

Sequence:

H-YHWYGYTPQNVI-OH

Cas No. :

Molecular Formula:

C₇₅H₉₇N₁₇O₁₉

Molecular Weight:

1540.67

Purity

95%+

Description

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.

Reference

• 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