Targeting EGFR Overexpression at the Surface of Colorectal Cancer Cells by Exploiting Amidated BODIPY ‐Peptide Conjugates

AbstractThree BODIPY ‐peptide conjugates designed to target the epidermal growth factor receptor (EGFR) at the extracellular domain were synthesized and their specificity for binding to EGFR was investigated. Peptide sequences containing seven amino acids, GLARLLT (2) and KLARLLT (3), and 13 amino acids, GYHWYGYTPQNVI (4), were conjugated to carboxyl BODIPY dye (1) by amide bond formation in up to 73% yields. The BODIPY ‐peptide conjugates and their “parent” peptides were determined to bind to EGFR experimentally using SPR analysis, and were further investigated using computational methods (AUTODOCK). Results of SPR, competitive binding, and docking studies propose that conjugate6 including the GYHWYGYTPQNVI sequence binds to EGFR more effectively than conjugates5 and7, bearing the smaller peptide sequences. Findings in human carcinoma HEp2 cells overexpressing EGFR showed nontoxic behavior in the presence of activated light (1.5 J/cm2) and in the absence of light for all BODIPYs. Furthermore, conjugate6 showed about 5 ‐fold higher accumulation within HEp2 cells compared with conjugates5 and7, localizing preferentially in the cell ER and lysosomes. Our findings suggest that BODIPY ‐peptide conjugate6 is a promising contrast agent for detection of colorectal cancer and potentially other EGFR over ‐expressing cancers.
Source: Photochemistry and Photobiology - Category: Science Authors: Tags: SPECIAL ISSUE RESEARCH ARTICLE Source Type: research