Nucleotide Analogs in Selection

Selectable genetic markers - Modified nucleotides can be used to select cells containing or lacking specific enzymes. Examples include the following:

> 6-Thioguanine - selects for cells lacking an active hypoxanthine-guanine phosphoribosyltransferase (HGPRT). Cells containing an active enzyme convert 6-thioguanine to a toxic compound.

> 5-Bromodeoxyuridine (BrdUrd) - can be used to select cells lacking thymidine kinase, which is needed to metabolize BrdUrd to a toxic metabolite.

> HAT Selection - The compounds hypoxanthine, aminopterin (see here), and thymidine (H,A, and T, respectively) can be used to select for cells having functional salvage pathways. Aminopterin inhibits dihydrofolate reductase, which blocks de novo purine and thymidine synthesis. Only cells which can utilize thymidine (pyrimidine salvage) and hypoxanthine (purine salvage) can grow in this medium.

See also: Drug Design, Salvage Routes to Deoxyribonucleotide Synthesis, Excessive Uric Acid in Purine Degradation, Biosynthesis of Thymine Deoxyribonucleotides