Domin B A, Mahony W B, Zimmerman T P
Experimental Therapy Department, Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709.
Biochem Biophys Res Commun. 1988 Aug 15;154(3):825-31. doi: 10.1016/0006-291x(88)90214-8.
The influx of 2',3'-dideoxythymidine into human erythrocytes was characterized to gain insight into the molecular properties of 3'-azido-3'-deoxythymidine which allow this latter nucleoside analog to permeate cell membranes by nonfacilitated diffusion (J. Biol. Chem. 262, 5748-5754 (1987]. The influx of 2',3'-dideoxythymidine was (1) nonconcentrative, (2) a linear function of permeant concentration (0.05 to 12 mM), and (3) insensitive to potent inhibitors of nucleoside transport and to permeants of either the nucleoside or nucleobase transporter. It is concluded that 2',3'-dideoxythymidine, like 3'-azido-3'-deoxythymidine, permeates the human erythrocyte membrane predominantly by nonfacilitated diffusion. This unusual characteristic of these two nucleoside analogs is attributed both to their lack of a 3'-hydroxyl moiety, a structural determinant which appears to be important for transport by the nucleoside carrier, and to their relatively high partition coefficients (greater than or equal to 0.2).
对2',3'-二脱氧胸苷进入人红细胞的过程进行了表征，以深入了解3'-叠氮基-3'-脱氧胸苷的分子特性，正是这些特性使后一种核苷类似物能够通过非易化扩散穿透细胞膜（《生物化学杂志》262, 5748 - 5754 (1987)）。2',3'-二脱氧胸苷的流入具有以下特点：(1) 非浓缩性；(2) 是渗透物浓度（0.05至12 mM）的线性函数；(3) 对核苷转运的强效抑制剂以及核苷或核碱基转运体的渗透物不敏感。得出的结论是，2',3'-二脱氧胸苷与3'-叠氮基-3'-脱氧胸苷一样，主要通过非易化扩散穿透人红细胞膜。这两种核苷类似物的这种不寻常特性既归因于它们缺乏3'-羟基部分（这一结构决定因素似乎对核苷载体的转运很重要），也归因于它们相对较高的分配系数（大于或等于0.2）。
