Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA.
School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71201, USA.
Molecules. 2021 Jan 23;26(3):593. doi: 10.3390/molecules26030593.
Through a simple 1,3-cycloaddition reaction, three BODIPY-peptide conjugates that target the extracellular domain of the epidermal growth factor receptor (EGFR) were prepared and their ability for binding to EGFR was investigated. The peptide ligands K(N)LARLLT and its cyclic analog cyclo(K(N)larllt, previously shown to have high affinity for binding to the extracellular domain of EGFR, were conjugated to alkynyl-functionalized BODIPY dyes and via a copper-catalyzed click reaction. This reaction produced conjugates , , and in high yields (70-82%). In vitro studies using human carcinoma HEp2 cells that overexpress EGFR demonstrated high cellular uptake, particularly for the cyclic peptide conjugate , and low cytotoxicity in light (~1 J·cm) and darkness. Surface plasmon resonance (SPR) results show binding affinity of the three BODIPY-peptide conjugates for EGFR, particularly for bearing the cyclic peptide. Competitive binding studies using three cell lines with different expressions of EGFR show that binds specifically to EGFR-overexpressing colon cancer cells. Among the three conjugates, bearing the cyclic peptide exhibited the highest affinity for binding to the EGFR protein.
通过简单的 1,3-环加成反应，制备了三种靶向表皮生长因子受体（EGFR）细胞外结构域的 BODIPY-肽缀合物，并研究了它们与 EGFR 的结合能力。肽配体 K(N)LARLLT 及其环状类似物 cyclo(K(N)larllt 先前被证明对 EGFR 的细胞外结构域具有高亲和力，通过铜催化点击反应与炔基功能化的 BODIPY 染料 和 偶联。该反应以高产率（70-82%）生成缀合物 、 和 。在过表达 EGFR 的人癌细胞系 HEp2 中的体外研究表明，这些缀合物具有高细胞摄取率，特别是环状肽缀合物 ，并且在光照（~1 J·cm）和黑暗条件下的细胞毒性较低。表面等离子体共振（SPR）结果表明，三种 BODIPY-肽缀合物对 EGFR 的结合亲和力，特别是对带有环状肽的 。使用三种 EGFR 表达水平不同的细胞系进行的竞争性结合研究表明， 特异性结合 EGFR 过表达的结肠癌细胞。在这三种缀合物中，带有环状肽的 对 EGFR 蛋白的结合亲和力最高。
