离体
体内
化学
连接器
癌症研究
配体(生物化学)
分子生物学
肽
发育不良
体外
受体
病理
生物化学
医学
生物
生物技术
操作系统
计算机科学
作者
Jing Chen,Juan Zhou,Zhaoshun Gao,Xue Li,Fa Wang,Xiyu Duan,Gaoming Li,Bishnu P. Joshi,Rork Kuick,Henry D. Appelman,Thomas D. Wang
标识
DOI:10.1021/acs.jmedchem.8b00405
摘要
Esophageal adenocarcinoma (EAC) is a molecularly heterogeneous disease that is rising rapidly in incidence and has poor prognosis. We developed a heterobivalent peptide to target detection of early Barrett's neoplasia by combining monomer heptapeptides specific for either EGFR or ErbB2 in a heterodimer configuration. The structure of a triethylene glycol linker was optimized to maximize binding interactions to the surface receptors on cells. The Cy5.5-labeled heterodimer QRH*-KSP*-E3-Cy5.5 demonstrated specific binding to each target and showed 3-fold greater fluorescence intensity and 2-fold higher affinity compared with those of either monomer alone. Peak uptake in xenograft tumors was observed at 2 h postinjection with systemic clearance by ∼24 h in vivo. Furthermore, ligand binding was evaluated on human esophageal specimens ex vivo, and 88% sensitivity and 87% specificity were found for the detection of either high-grade dysplasia (HGD) or EAC. This peptide heterodimer shows promise for targeted detection of early Barrett's neoplasia in clinical study.
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