von Baeyer H, Neitzel H, Nündel M, Riedel E, Schultis H K
Freie Universität Berlin, Institut für Biochemie, Klinikum Rudolf Virchow, Germany.
Int J Clin Pharmacol Ther Toxicol. 1993 Aug;31(8):382-6.
Covalent coupling of thymidine and azidothymidine (ZIDOVUDINE) to epsilon-amino groups of lysine side chains of LDL-Apo B is described. This procedure generates LDL-nucleoside particles that exhibits affinity solely for the scavenger receptor pathway on macrophages which is demonstrated by cell culture experiments. Autoradiography shows that 3H-thymidine, as representative of nucleosides, is delivered to the cell nucleus. Hence internalization, lysosomal cleavage and triphosphorylation of thymidine evidently had occurred. The application of this new method of drug targeting is macrophage selective inhibition of HIV-reverse transcriptase in AIDS.
描述了胸苷和叠氮胸苷（齐多夫定）与低密度脂蛋白 - 载脂蛋白B赖氨酸侧链的ε - 氨基基团的共价偶联。该过程产生仅对巨噬细胞上的清道夫受体途径具有亲和力的低密度脂蛋白 - 核苷颗粒，这在细胞培养实验中得到了证明。放射自显影显示，作为核苷代表的3H - 胸苷被递送至细胞核。因此，胸苷的内化、溶酶体裂解和三磷酸化显然已经发生。这种新的药物靶向方法的应用是在艾滋病中对HIV逆转录酶的巨噬细胞选择性抑制。
