Guanosine triphosphate , drug

Paclitaxel is an alkaloid ester derived from the Pacific yew (Taxus brevifolia) and the European yew (Taxus baccata). The drug functions as a mitotic spindle poison through high-affinity binding to microtubules with enhancement of tubulin polymerization. This promotion of microtubule assembly by paclitaxel occurs in the absence of microtubule-associated proteins and guanosine triphosphate and results in inhibition of mitosis and cell division. 

Interest in paclitaxel was stimulated by the finding that the drug possessed the unique ability to promote microtubule formation at cold temperatures and in the absence of guanosine triphosphate (GTP). It binds specifically to the P-tubulin subunit of microtubules and antagonizes the disassembly of this key cytoskeletal protein, with the result that bundles of microtubules and aberrant structures derived from microtubules appear in the mitotic phase of the cell cycle. Arrest in mitosis follows. Cell killing (CK) is dependent on both drug concentration and duration of cell exposure. 

Figure 23.17 shows some antiviral drugs related to the purine base guanosine. These drugs work by blocking the synthesis of viral DNA or by becoming incorporated into viral DNA, thus preventing its transcription. In living systems, the triphosphate of guanosine becomes incorporated in a DNA strand linked to the strand via its 5 and 3 positions (Fig. 23.18). Two such DNA strands give the DNA double helix.

Acyclovir is an antiviral drug used to treat herpesvirus infection. The basis of its action is that acyclovir resembles part of the guanosine nucleoside and is phosphorylated by the viral enzyme, deoxypyrimidine kinase. The phosphorylated triphosphate form of acyclovir is an inhibitor of the herpesvirus DNA polymerase. A related compound, ganciclovir, H2N works similarly. Uninfected cells do not efficiently phosphorylate acyclovir and ganciclovir, so DNA replication and vims growth are inhibited selectively in infected cells. 

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