Department of Biochemistry, School of Biological Science and Technology, Central South University, Changsha, 410013, Hunan, China.
Expert Opin Investig Drugs. 2011 Dec;20(12):1583-9. doi: 10.1517/13543784.2011.632407.
Interferon-alpha (IFN-α) is the traditional therapeutic agent for chronic myeloid leukemia (CML). The molecular mechanism of IFN-α efficacy in the treatment of CML is not fully clear.
To identify the peptides and/or proteins that bind to the proteins specifically expressed on the surface of IFN-α-sensitive CML cells by using a phage display library.
DESIGN/METHODS: IFN-α-sensitive KT-1/A3 cells were used as the target, and IFN-α-resistant subline KT-1/A3R was used as absorber for phage display biopanning. The positive phage clones were identified by enzyme-linked immunosorbent assay and flow cytometry. The peptides were deduced from their DNA sequences.
Multiple clones showed high binding efficiency to KT-1/A3 cells compared with that of the other leukemia cells. One of the peptides, KLWVIPQ, has a partial amino acid sequence homology with the C-terminal domain of E3 ubiquitin-protein ligase.
This study presents the identification of specific heptapeptides that bind to IFN-α-sensitive KT-1/A3 cells. The cancer-selective ligands provide novel strategies for early and differential diagnoses, as well as potential targeted drug delivery.
干扰素-α（IFN-α）是治疗慢性髓性白血病（CML）的传统治疗药物。IFN-α 治疗 CML 的疗效的分子机制尚不完全清楚。
通过噬菌体展示文库鉴定与 IFN-α 敏感的 CML 细胞表面特异性表达的蛋白质结合的肽段和/或蛋白质。
设计/方法：以 IFN-α 敏感的 KT-1/A3 细胞为靶细胞，以 IFN-α 耐药亚系 KT-1/A3R 为吸收剂进行噬菌体展示生物淘选。通过酶联免疫吸附试验和流式细胞术鉴定阳性噬菌体克隆。从 DNA 序列推导肽段。
与其他白血病细胞相比，多个克隆对 KT-1/A3 细胞表现出高结合效率。其中一个肽段 KLWVIPQ 与 E3 泛素蛋白连接酶 C 末端结构域具有部分氨基酸序列同源性。
本研究鉴定了与 IFN-α 敏感的 KT-1/A3 细胞结合的特异性七肽段。这些具有肿瘤选择性的配体为早期和差异诊断提供了新的策略，以及潜在的靶向药物输送。
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