Thomas Joshua D, Hofer Thomas, Rader Christoph, Burke Terrence R
Laboratory of Medicinal Chemistry, CCR, NCI, NIH, Frederick, MD 21702, USA.
Bioorg Med Chem Lett. 2008 Nov 1;18(21):5785-8. doi: 10.1016/j.bmcl.2008.09.078. Epub 2008 Oct 14.
A flexible, trifunctional poly(ethylene glycol)-succinamide-Lysine-Lysine-maleimide (PEG-SU-Lys-Lys-mal) linker was employed to simultaneously allow biotin tagging and cell-surface targeting through an integrin alpha(4)beta(1)-binding peptidomimetic that was regiospecifically conjugated to an IgG1-derived Fc fragment with an engineered C-terminal selenocysteine residue. The resulting antibody derivative mediates Fc receptor binding by virtue of the Fc protein and selectively targets cancer cells expressing human integrin alpha(4)beta(1). The PEG-SU-Lys-Lys-mal linker may have general utility as an organic tether for the construction of antibody-drug conjugates.
使用一种柔性三功能聚乙二醇 - 琥珀酰胺 - 赖氨酸 - 赖氨酸 - 马来酰亚胺（PEG - SU - Lys - Lys - mal）连接子，通过一种与工程化C末端硒代半胱氨酸残基的IgG1衍生Fc片段区域特异性缀合的整合素α(4)β(1)结合拟肽，同时实现生物素标记和细胞表面靶向。所得抗体衍生物凭借Fc蛋白介导Fc受体结合，并选择性靶向表达人整合素α(4)β(1)的癌细胞。PEG - SU - Lys - Lys - mal连接子作为构建抗体 - 药物偶联物的有机连接体可能具有广泛用途。
