title: 2',3'-Dideoxythymidine permeation of the human erythrocyte membrane by nonfacilitated diffusion.
abstract: 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).
authors.affiliation: Experimental Therapy Department, Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709.
authors.forename: B A
authors.initials: BA
authors.lastname: Domin
authors.forename: W B
authors.initials: WB
authors.lastname: Mahony
authors.forename: T P
authors.initials: TP
authors.lastname: Zimmerman
mesh_terms: D000998:Antiviral Agents / Q000097:blood*; D001692:Biological Transport / Q000187:drug effects; D004058:Diffusion; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D009705:Nucleosides / Q000494:pharmacology; D018119:Stavudine; D013936:Thymidine / Q000031:analogs & derivatives* / Q000097:blood; D014316:Tritium
chemical_list: D000998:Antiviral Agents; D009705:Nucleosides; D014316:Tritium; D018119:Stavudine; D013936:Thymidine