Departamento de Química Orgánica e Inorgánica and Instituto Universitario de Biotecnología de Asturias, Universidad de Oviedo, 33006 Oviedo, Asturias, Spain.
Bioorg Med Chem. 2013 Dec 15;21(24):7779-89. doi: 10.1016/j.bmc.2013.10.013. Epub 2013 Oct 28.
C-3-substituted 25-hydroxyvitamin D3 analogues were synthesized as tools to directly measure levels of vitamin D in biological samples. The strategy involves vinyloxycarbonylation of the 3β-hydroxy group and formation of a carbamate bond with a hydroxyl or amino group at the end of the alkyl chain. Biotinylated conjugates of synthesized derivatives were generated to be linked with vitamin D binding protein (DBP). The spacer group present in the alkyl chain is important in the binding of antibodies to the analogue-DBP complex. When compared to 25-hydroxyvitamin D3-DBP, the binding of some antibodies to the analogue-DBP complex of the 25-hydroxyvitamin D3 derivative 10 that posses an 8-aminoctyl alkyl chain is significantly reduced, but this analogue displaced [26,27-(3)H]-25-hydroxyvitamin D3 from DBP. In contrast, the 8-hydroxyoctyl alkyl chain analogue 9 showed less displacement.
C-3 取代的 25-羟基维生素 D3 类似物被合成作为直接测量生物样品中维生素 D 水平的工具。该策略涉及 3β-羟基的乙烯氧羰基化以及与烷基链末端的羟基或氨基形成氨基甲酸酯键。合成衍生物的生物素化缀合物被生成以与维生素 D 结合蛋白（DBP）结合。烷基链中存在的间隔基团对于抗体与类似物-DBP 复合物的结合很重要。与 25-羟基维生素 D3-DBP 相比，一些抗体与具有 8-氨基辛基烷基链的 25-羟基维生素 D3 衍生物 10 的类似物-DBP 复合物的结合显著减少，但该类似物将[26,27-（3）H]-25-羟基维生素 D3 从 DBP 中置换出来。相比之下，8-羟辛基烷基链类似物 9 显示出较小的置换。
