羧基封端的 PAMAM-SN38 缀合物：合成、表征和体外评价。
Carboxyl-terminated PAMAM-SN38 conjugates: synthesis, characterization, and in vitro evaluation.
机构信息
Departments of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84108, USA.
出版信息
Bioconjug Chem. 2010 Oct 20;21(10):1804-10. doi: 10.1021/bc100094z.
In this work, carboxyl-terminated PAMAM G-3.5 was covalently attached to SN38 via glycine and β-alanine spacers. The conjugates were stable at pH 7.4 and moderately hydrolyzed in cell culture media and rat plasma. Similarly to SN38 but to a lesser extent, both conjugates inhibited proliferation of human colorectal cancer HCT-116 cells, arrested the cell cycle in the G(2)/M phase, and led to nuclear fragmentation. However, activity of the conjugate with glycine spacer (IC(50) = 129 nM) was higher compared to that of the β-alanine linked conjugate (IC(50) = 387 nM). These PAMAM-SN38 conjugates have the potential for targeted therapy of colorectal carcinoma.
在这项工作中，通过甘氨酸和β-丙氨酸间隔物将羧酸末端的 PAMAM G-3.5 共价连接到 SN38 上。在 pH 7.4 时，这些缀合物稳定，在细胞培养基和大鼠血浆中适度水解。与 SN38 类似，但程度较轻，两种缀合物均抑制人结肠直肠癌细胞 HCT-116 的增殖，将细胞周期阻滞在 G(2)/M 期，并导致核碎裂。然而，具有甘氨酸间隔物的缀合物的活性（IC(50) = 129 nM）高于与β-丙氨酸连接的缀合物的活性（IC(50) = 387 nM）。这些 PAMAM-SN38 缀合物具有用于结直肠癌靶向治疗的潜力。
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